Protocols for Clinical Practice R

Home , Fluorodeoxyglucose (18F), Immunoscintigraphy, Iodocholesterol, SeHCAT

APPENDIX ONE Protocols for clinical practice R. Mistry

This is not intended to be a textbook of nuclear one investigation but we have included methods medicine science or technology. We have, howev• that we use and are generally found to be wark• er, included an outline of the major procedures for able in routine clinical use. Moredetails of some reference. Needless to say, a more complete de• techniques will be found where appropriate in scription should be studied before starting a new individual chapters. method. There is more than one way of doing any Radiopharma- Route of Patient ceutical/s and Patient administration Quantitative preparation dose position and delay Equipment Technique analysis Comment

Thallium myocardial scan None for rest- 201Tl chloride Supine I. V oinjection Standard field 10 min images Varies from Pharmacological ingstudy 1.5-2mCi (at peak of of view gamma screening the background stress with Maximum exer- (50-75 MBq) stress); con- camera, GAP extra-cardiac subtraction to dipyridamole eise (bicycle tinue exereise collimatoro structures with various filters may be substi- ergometer or for 1 minute, Computer Iead sheet. and count den- tuted for exer- treadmill) for image after a ViewsareA, sity measure- eise oSPECT may stress study delay of 5 min- LA0(45and ments be substituted utes for stress 55°), LL. De- and20 layed views minutes for a at4 hoursas reststudy indicated

99'"Tc MIBI myocardial scan

Exercise as 300-500MBq Supine I. V 0 injection at Standard field 10 min images Rest and stress per thallium peak of exer- of view gamma (gated) view- maybeper- scan eise; continue camera with ANT, LA045 formed on the exercise for 1 GAPorhigh LA070 or ellip- sameday mino Image at resolution col- tical tomogra- 1-2 hours fol- limatorand phy 180° using lowing computer and high resolution gatingunit collimator

For rest MIBI Wait for 48 hrs 300-500MBq Supine Patients rested Standard field + elliptical180° following for 1 hour prior of view Gamma tomography Exercise study to injection camera with usinghigh GAPorhigh resolution resolution col- collimator limatorand computer and gatingunit

Multiple gated blood pool scan None 20mCi (750 Supineo Careful i.vo in- Standard field Image to attain Measure ejec- MBq) Prone for jection or bolus of view gamma a count density tion fraction 99mTc-Auto- LPO firstpass study camera, high of greater than routinelyo logous red performed resolution, 250 counts/ There are many blood cells simul- GAPorslant pixel over the otherpar- Iabelied in vivo taneouslyo hole collimator left ventricle in ameters which or in vitro Nodelay and computer eachframeo maybeused withRwave Viewsare trigger RAO,A,LAO, possibly LPOo RepeatLAOo

is is

over) over)

ven-

scan. scan.

usually usually

with with

is is

(cont'd (cont'd

tilation tilation

done done

This This

helpful helpful

tomography tomography

emission emission

Singlephoton Singlephoton

deter-

ejec-

relative relative

perfu-

patients patients

in in

compro-

in in

fraction fraction

misedlung misedlung

function. function.

sion sion

with with

pulmonary pulmonary

mining mining

arterial arterial

Useful Useful

shunting shunting

tion tion

Measure Measure andL-R andL-R

Notroutine Notroutine

in in

P, P,

A. A.

and and

pro-

or or

A, A,

with with

during during

45° 45°

auto-

of of

count count

routine routine

prob-

View View

frame, frame,

sequence sequence

cells cells

blood blood

images images

to to

study study

RAO RAO

acquisition acquisition

LL,RPO, LL,RPO,

000 000

LAO LAO

histogram histogram

Iist, Iist,

using using

min min

LPO LPO

RL, RL,

images images

pool pool

gated gated

ceed ceed

500 500

blood blood

dependson dependson

If If logousred logousred

lern; lern;

clinical clinical mode. mode.

or or

in in

data data

firstpass firstpass imaging imaging Rapid Rapid

A, A,

70° 70°

5 5

for for

field field

R R

com-

GAP GAP

with with

gamma gamma

with with

sensi-

trigger trigger

children.) children.)

or or

resolution resolution

view view

resolution resolution

collimator collimator

GAPorHigh GAPorHigh

camera camera

LFOVgamma LFOVgamma

Possibly Possibly

Computer. Computer.

tivity tivity

small small

collimator collimator

wave wave

(High (High

high high

Standard Standard

Possibly Possibly collimator. collimator.

camera camera

of of

camera camera puter puter

high high

collimator. collimator.

of of

Standard Standard

not not

of of

bolus bolus

delay delay

injec-

No No

Do Do

use use

v. v.

i.v. i.v.

No No

lying lying

breathing breathing

i. i.

saline saline

during during

injection injection

V. V.

delay delay

syringe. syringe.

drawback drawback

tion tion supine. supine.

quiet quiet bloodinto bloodinto

while while

Slow Slow

flush. flush. Rapid Rapid

(Avoid (Avoid

with with

3hourdelay 3hourdelay

catheters). catheters).

indwelling indwelling

I. I.

or or

sitting sitting

Lying Lying

Supine Supine

on on

or or

mac-

cells cells

mTc-

of of

chil-

micro-

or or

MBq) MBq)

dose dose

of of

surface surface

Ci(350 Ci(350

mCi mCi

blood blood

basis basis

autologous autologous

mTc-pyro-

spheres spheres

roaggregates roaggregates

(30-100 (30-100

ticles ticles Iabelied Iabelied

200000J:r-

approximately approximately

1-3 1-3

the the

drens' drens'

(Reduce (Reduce

body body

area) area)

20mCi(750 20mCi(750

red red

pertechnetate pertechnetate

or or phosphate phosphate

MBq) MBq)

equivalent equivalent 99m_Tc-

MBq) MBq)

10m 10m

imaging imaging

angiogram angiogram

scan scan

infarct infarct

lung lung

isotope isotope

pass pass

None None Perfusion Perfusion

(Children (Children

None None First First

sedated) sedated)

Myocardial Myocardial None None (cont'd) Radiopharma- Routeof Patient ceutical/s and Patient administration Quantitative preparation dose position and delay Equipment Technique analysis Comment

Ventilation scan None 81 mKr from 81 Rb Lying or Inhalation LFOVGamma 81 mKr-views Not routinely, This examination generator or sitting either before camera with obtained im- but use is in- is usually done 10-20mCi perfusion scan GAP collimator mediately after creasing with a perfusion 133 133 ~350-700MBq) ( Xe) or ( Xe) or each perfusion Jung scan. The 33Xe via simultaneously mediumcol- scan view with combination dispenser, ( 81 Kr). No limator (81 mKr) camera peaked of these tests 99mTcDTPA delay toSlmKr. increases the aerosol or 99mTc 133Xe - view de- sensitivity and Technegas pending on cli- specificity of the nical problem. findings ( 99mTcDTPA aerosolor Technegas- views immediately followed by 99mTc MAA perfusion at 1-2 hours later.)

Radionuclide venogram None 2 doses of 4mCi Supine, Simultaneously Large field of a With tourni- Nil Performed in 99mTc (150 camera over i.v. bilateral in viewgamma quets on, move conjunction with MBq) Iabelied abdomenfor dorsum of feet, camera with patient to Jung scan microspheres inferior vena leave tourni- GAP obtain sequen- or macroaggre- cava flow, quets on collimator tial6000-10 000 gates orover around ankles count images of calves for leg calves, knees, venogram thighs and abdomen. Re- peat with tour- niquets off, and again afterJung scan or after leg raising

in-

to to

may may

over) over)

inject inject

are are

AV AV

must must

in-

to to

urine urine

above above

accu-

blood blood

and and

GFR GFR

If If

calculation calculation

with with

care care

measured measured

UV/P UV/P

the the

(cont'd (cont'd

y. y.

calculated calculated

taken taken

be be

formula formula

from from

cluded cluded

collections collections

time time

samrvles samrvles

exact exact

rate rate

volume volume

be be

Great Great shunt shunt

peripheral peripheral

Maybecom-

bined bined

mid-thigh mid-thigh

Relatively Relatively

sensitive sensitive

of of

cal-

and and

be-

GFR GFR

at at

Cr Cr

stan-

the the

20% 20%

1/2 1/2

points points

log log

0 0

sam-

Plot Plot

ona ona

> >

sym-

adjacent adjacent

should should

orbe-

and and

estimate estimate

limbs limbs

semi semi

Calculate Calculate

Time= Time=

intercept intercept

and and

culateT culateT

on on

EDTA. EDTA.

counts/time counts/time ples ples

plasma plasma

dard dard

radioactivity radioactivity

measure measure

Centrifuge Centrifuge

two two

None None

tween tween

metrical metrical

points points

limb limb

tween tween

between between

notbe notbe

difference difference

There There

N/A N/A

3 3

at at

2, 2,

has has

hours hours

cover cover

point point

limbs limbs

ml ml

at at

daily daily

8 8

blood blood

to to

func-

count count

images images

the the

10 10

cm cm

samples samples

injection injection

equilibra-

5 5

bolus bolus

severely severely

and and

lower lower

micro-

6 6

renal renal

tion tion

at at

(extra (extra

impaired) impaired)

samples samples

if if

venous venous and4hours and4hours spheres spheres

the the

Timed Timed

images images

of of

after after

immediately immediately

300000 300000

tion tion

after after

each each

Spotcounts Spotcounts

second second

heart heart

passed passed

until until

Sequential2 Sequential2

of of

and and

count-

with with

gamma gamma

field field

collimator collimator

camera camera

(well (well

scintillation scintillation

counter) counter)

ing ing

Sample Sample

GAP GAP

LFOV LFOV camera camera

scintillation scintillation

recorder recorder

detector detector

Collimated Collimated

withGAP withGAP

view view collimator collimator

Large Large

sam-

and and

for for

injec-

arm arm

via via

2 2

in-

com-

or or

v. v.

from from

Left Left

antecu-

i. i.

First First

assess-

for for

vein vein

delay delay

5-10min-

after after

opposite opposite

tion. tion. plete plete

Careful Careful

hours hours ple ple

needle needle

catheter catheter

injection injection

syringeand syringeand Intra-arterial Intra-arterial

utes utes

I.V. I.V.

ment ment

nominate nominate

vein vein

SVC SVC ment. ment.

antecubital antecubital bital bital

Right Right

SVC SVC

pos-

over over

Resting Resting

Supine Supine

itioned itioned

mediastinum mediastinum

Supine Supine

camera camera

Supine, Supine,

/ocalization /ocalization

i.v. i.v.

2-5 2-5

A. A.

1 1

1.4 1.4

MBq MBq

~4MBq) ~4MBq)

donein donein

mTc mTc

13 13

orlung orlung

labelled labelled

etc., etc.,

(50-150 (50-150

liver, liver,

be be

(100-200 (100-200

EDT EDT

~-tCi ~-tCi

or or

thrombus thrombus

1 1

Cr Cr

mTc mTc

Child2MBq, Child2MBq,

lnfant1 lnfant1 Adult3MBq, Adult3MBq,

approx. approx.

microspheres microspheres

spheres, spheres, (500000 (500000

MBq) MBq)

mCi) mCi)

12s

fibrinogen fibrinogen

scan, scan, 100 100

MBq) MBq)

mCi mCi

with with

May May

maceutical. maceutical. conjunction conjunction

radiophar-

bone, bone,

Any

labelled labelled

' '

in-

venogram venogram

fibrinogen fibrinogen

fi/tration fi/tration

perfusion perfusion

may may

thigh thigh

cm cm

Mark Mark

from from

5 5

or or

to to

thyroid thyroid

Lugals Lugals

at at

duringan duringan

1-/abel/ed 1-/abel/ed

None None

Glomerular Glomerular

None None

Peripheral Peripheral

125 Block Block

arteriogram arteriogram

tervals tervals

ankle ankle

legs legs with with

lodine. lodine.

be be

None None Mediastinal Mediastinal

of of

may may

after after

and and

early early

reduce reduce

effect effect

dose dose

bladder bladder

+ + + +

an an

to to

image image

obtained obtained

diuretic diuretic

Frusemide Frusemide

Warnpatient Warnpatient

study study

bladder bladder

frequently frequently

empty empty

Fluids Fluids

flow flow

be be

Usinglarge Usinglarge

doses, doses,

Comment Comment

dif•

% %

per•

of of

uptake uptake

and and

blood blood

transit transit

Output Output

and and

washout washout

paren•

divided divided

renal renal

back•

of of

pelvis. pelvis.

efficiency efficiency

rate rate

from from

Measure Measure

centage centage

time time

chymal chymal

relative relative GFR, GFR,

Analysisof Analysisof flow, flow,

Pviews Pviews

meanofAand meanofAand

tracted tracted

geometric geometric

with with

groundsub•

ferential ferential

Analysis Analysis

Quantitative Quantitative

analysis analysis

on on

min min

5, 5,

min, min,

1 1

views views

view view

for for

2 2

time time

and and

views views

and and

at at

10 10

kidneys kidneys

400000 400000

views views

minutes. minutes.

zoom zoom

images. images.

time, time,

time time

fixed fixed

20 20

terior terior

0 0

indicated indicated

min, min,

min min

for for

5 5 at at Image Image

Bladder Bladder

atend atend

10, 10,

fixed fixed

counts counts

(an (an

transplant) transplant)

0-30s, 0-30s,

Posterior Posterior

computer computer

using using

camera/ camera/

as as posterior posterior

oblique oblique

lateral lateral

Anterior Anterior

Technique Technique

5 5

GAP GAP

with with

dynamic dynamic

with with

resolution resolution

per per

mTcDTPA mTcDTPA

renal renal

As As

Computer Computer

collimator. collimator.

LFOVgamma LFOVgamma camera, camera,

high high

collimator collimator

Equipment Equipment

camera camera

LFOVgamma LFOVgamma

with with

injec•

dynamic dynamic

scan scan

hour hour

of of

Immedi•

bolus bolus

3 3

per per

imaging imaging

delay delay

mTcDTPA mTcDTPA

V. V.

renal renal

As As

tion. tion.

ate ate

I. I.

delay delay

I. I.

Route Route

and and

administration administration

to to

re•

or or

um•

with with

dy-

I I

mTc mTc

renal renal

bent bent

per per

Iordosis Iordosis

DTPA DTPA

namic namic

with with

As As

supine, supine,

clining clining

Sitting Sitting

reduce reduce

knees knees

bar bar

position position

Supine Supine

Patient Patient

washaut washaut

MBq MBq

with with

mCi, mCi,

and and

Hip•

dynamic dynamic

100 100

(10 (10

mTc•

(2 (2

I I

DTPA DTPA

scan scan

mTcMAG3 mTcMAG3

mTc mTc

Frusemide Frusemide

A A

99 123

MBq) MBq)

an an

per per

mTc mTc

mCi, mCi,

with with

renal renal

As As

pur pur 3 3

75MBq) 75MBq)

(b) (b)

(a) (a)

175 175

DTP DTP

DMSA DMSA

MBq)

5mCi(200 5mCi(200

Radiopharma•

dose dose

ceuticalls ceuticalls

scan scan

to to

1 1

mg/ mg/

mg mg

mTc mTc

i.v. i.v.

For For

kg kg

2 2

image image

renal renal

20 20

renal renal

kg-

min-

Inject Inject

10 10

per per

kg kg

prior prior

fluid fluid

< <

renal renal

with with

20 20

as as

A. A.

10 10

mg mg

ml ml

adults. adults.

if if

min min

> >

kg kg

if if

children children

for for

(0.5 (0.5

bodyweight bodyweight

Frusemide Frusemide

DTP DTP

scan scan

Dynamic Dynamic

utes utes

dynamic dynamic

First First

study study

Dynamic Dynamic

200 200

30 30

Static Static

None None

preparation preparation

Patient Patient (cont'd) (cont'd) to

the

Try

vice

over)

the

priv•

equip•

empty

Xß

suit•

chil•

years

remote

for dose.

fre•

and

tech•

patient

for with

reduce

and

males.

(B))

(cont'd

Only for

older

(A)

operate

passed)

remainder

day

Advise bladder to

drink bladder

control quently

acy. able nicians Fernale and dren. versa

ment females maximum

(ml)

counts

urine

be•

activ•

volume

Bladder

(ml

Sacro•

(bladder

kidneys

during

activity

ureters

after

Residual none. Routinely

micturition iliac fore, and quantitation indicated

Measure

change ity

and

be•

for of

cover body

for

(B)

(A)

an•

min•

pos•

into

device

An•

view

count

and

data

for

re•

and

density

time

bladder ehest.

during

post

for

body

whole

computer

minute

Record to recorded 1 utes corded

micturition terior for 1 remainder urinal 750,000 Fixed volumere• the posteriorly emptied disposable teriorly terior review images

bladder corded. Anterior equivalent count imaging Bladder fore, image and

im•

col•

high

with with

pinhole

body

device

collimator

computer

LFOVgamma

camera camera GAP computer

LFOVgamma

LFOVgamma resolution

and camera, whole collimator converging limator

forhips aging

with

dynamic

scan

30-60min•

injection.

delay

per

mTcDTPA

As renal

ute LV.

moredelay

3hours

be•

over

withgamma

hind

commode renalareas camera Sittingon

N/A

bladderand

Lyingor

sitting

with

MBq)

dynamic

15mCi

DTP

scan

(35

per

mTcDTPA

mTc

As renal

mCi

Diphosphonate

(MDP) (500MBq)

Methylene 99mTc•

reflux

volume

mTc

after

dy-

urine

min-

per

scan

20 with

may

time

patient

Vesico-ureteric

utes

scan

First

DTPA dynamicrenal Residual

performed

standard Bonescan

namic99mTc This renal

Hydration the

of injection site

for

detect

images

whole

particular

association

packsmaybe used

symptomatic andmeasure CSF!eakage

Nasalorear

assessment of

Maybedone with body

in Comment

additional

none

routinely

Not

Routinely Quantitative

analysis

LL,

sing-

hours

side

time.

images

con-

views

cisterns only)

count

RL,

Com-

hours,

min

same

view

hours,

(A,

at2 6

Vertex)

ages (15 5minuteim-

tralateral

side. Je for

parison

delayed Technique ofinvolved

500000

field

stan-

de-

gamma

with

area

field

examined.

converging

view

highenergy

of camera collimator

Standard

size or collimator

pendingon

be dard Equipment Highresolution

LFOV

camera,

for

scan

injec-

for

within

magna

image

Begin

then

Static

pool'

hone

delay

(foot

bolus

sec

delay

minute

hourdelay

cisterna

Intrathecal

injection: phase,

'blood

images static

menced

1 study. hour

immediately

for'flow' imagescom-

tion

hands)

imaging

injection

-40 I.

Routeof

administration and

site

Lying

position camera

positioned under/over

Patient

Specific

MBq)

mTc-

and

site

(500

f!Ci

mCi

In-DTPA

specific

FOMBq)

500

15 MDP

dose ceutical/s

Radiopharma-

for

scan

bone

phase

None

Cisternogram

preparation

None

3 Patient

(cont'd) Brain scan None 20mCi Lying I. V. rapid bolus Standard field 1 second im- Time activity Delayed views r50MBq) injection. No of view gamma ages for 1 min curves plotted may be helpful in 9mTcGHAor delay for dy- camera with in the anterior from ROI over equivocal cases, equivalent namic study. 90 GAP collimator or vertex view the two hemi- patients sus- minute delay and computer during the first spheres pected of having for static scan pass. Equilib- subdural haema- rium blood toma should be pool image im- scanned at3 mediately after hours post dynamic scan injection. SPECT for300000 imagingmay counts. At 90 contribute. minutes 300000 count images in A,P,LL,RL and vertex positions SPECT Brain 10mCi Supineina I.V. wait20 LFOVgamma 64, 20 second ~50MBq) dimly lit min before cameraand images using mTcHMPAO room, with starting scan computer for circular 99mTcECD I. V. cannula tomography tomography for 5-10 mins with a high around 360° prior to injec- resolution (using 64 x 64 tion collimator matrix) recon- struct 2 pixel thick slices. Thyroid scan None 5mCi~180 Supine LV. injection Standard gam- Wash oeso- Measureup- Scanmustbe MBq) 9 mTc. with neck with 20 minute ma camera phaguswith take using ROI combined with Pertechneta te extended delay (99mTc with pinhole or glass of water; around thyroid manual examin- or500t-t Ci pertechneta te) 'snout' collima- anterior view and also a back- ation of the (20 MBq) 1231 or oral adminis- tor computer if with maximum groundROI gland ± ultra- sodium iodide tration with 3 measuring up- magnification and express as sound hourdelay take simul- 100 000 counts percentage of a e231) taneously. Use for 15 minutes. standard or the parallel hole LAOandRAO syringe meas- GAP collimator if indicated. ured in a thyr- for retrosternal Repeatwith oid phantom at extensions 57Co marker on a set distance nodule or from the gam- suprasternal macamera notch if indicated

(cont'd over) (cont'd) Radiopharma- Routeof Patient ceuticalls and Patient administration Quantitative preparation dose position and delay Equipment Technique analysis Comment Perchloratedischarge As per thyroid As per thyroid As perthy- As per thyroid As per thyroid GiveKC104 Measureup- scan using 1231 scan using 1231 roid scan scan using 1231 scan using 1231 1 g orally; im- take ateach using 1231 age the thyroid point and plot at constant dis- ongraph tance at 15 mi- paper. 10% nute intervals discharge forone hour of 1231 or more is abnormal indicating fai- Iure of organification

Whole body scan for thyroid cancer 4 weeks off T4 5-15 mCi {180- Lying Oral adminis- LFOVgamma 5minute im- Notusual Simultaneous or 2 weeks off 550 MBq) 311- tration; 72 camerawith ages to cover serum thyro- T3 replacement sodium iodide hours delay hi~henergy wholebody globulin Ievels therapy with a co limator or will improve low iodine diet; whole body im- accuracy serumTSH aging device Ievel above 40 mUml- 1

Adrenal scan

Renal outline 250 ~tCi Prone I. V. 7 day de- LFOVgamma At7 days a 15 The percentage lodocholesterol and depth may ~10MBq) lay, repeat at 14 camerame- minimageis uptake in each scanmaybe bemarked by 5Se methyl days diumenergy obtained cen- glandmaybe made after5 prior imaging cholesterol1-2 high sensi- tred over the made measur- days of suppres- with 99mTc- mCi (35-75 tivity collimator upperpoles ing the syringe sion with dexa- DMSAor MBq) of 1311- and computer containing methasone for 99mTc-DTPA iodocholesterol 75Se-cholesterol detection of is alternative and depth aldosterone correction secreting tumour

over) over)

presence presence

test test

(cont'd (cont'd

during during

ofsymptoms ofsymptoms

Record Record

over over

mid-

ac•

total total

time time

oeso•

of of

lower lower

curves curves

meas-

and and

to to

with with

for for

dis-

of of

ROI ROI

in in

record record

stomach. stomach.

of of

and and

upper, upper,

ROI ROI

tivity tivity

changing changing

oesophagus oesophagus phaguswith

Optimize Optimize

and and stomach stomach

image image

transit transit

Measure Measure

thirds thirds and and

oesophagus oesophagus

die die

Analyse Analyse for for

activity activity

stimulant stimulant

rate rate

charge charge

urerate urerate

accumulated accumulated

Using Using

activity activity

glands, glands,

in•

as as

for for

the the

mag-

10 10

(acid (acid

15 15

of of

start. start.

in in

im-

anter-

second second

abdo•

at at

in in

exclude exclude

at at

lemon) lemon)

pos-

images images

show show

include include

lesion lesion

anterior anterior

image image

minutes minutes

hinder hinder

images images

gland gland

with with

30 30

to to

anterior anterior

or or

to to

of of

collection. collection.

upper upper

afteF afteF

glands glands

10 10

minutes. minutes.

given given

mass mass

minute minute

minal minal

pressure pressure

flatable flatable

100mmHg 100mmHg

20mm,40mm, 20mm,40mm,

60mm,80mm, 60mm,80mm, view view

images images

then then

abdomen/ehest abdomen/ehest

oesophagus, oesophagus, retention retention

activity activity

erect erect

Single Single

for for

second second

stomach. stomach. and and

sitioned sitioned

oesophagus oesophagus iorly iorly

bolus bolus ofthe ofthe

camera camera

suspected suspected

nified nified Swallowed Swallowed

min min

is is

drop drop

data data

If If

Continuous Continuous Stimulant Stimulant 15 15

all4 all4

1 1

neck neck

ages ages

col-

field field

with with

gamma gamma

with with

view view

computer computer

cameraand cameraand

LFOVgamma LFOVgamma

computer computer

LFOVgamma LFOVgamma

camera camera

resolution resolution computer computer

limatorand limatorand

GAPorhigh GAPorhigh

camera camera

of of

Standard Standard

No No

adminis•

injection. injection.

V. V.

tration. tration.

delay delay

Oral Oral

Nodelay Nodelay

I. I.

if if

Re-

does does

neck neck

erect erect

er er

abdominal abdominal

bind bind

notreach notreach

peat peat

stomach stomach Supinewith Supinewith

bolus bolus Supine. Supine.

with with

extended extended

Supine Supine

in in

sul-

(20 (20

mTc mTc

squash squash

mTc mTc

acidified acidified

water water

9 9

colloid colloid

[!Ci [!Ci

[!Ci [!Ci ml ml

ml ml

phur phur

orange orange

MBq) MBq)

15 15

studies studies

300 300

phur phur 500 500

MBq) MBq)

500 500

pertechnetate pertechnetate

5mÖ~180 5mÖ~180

MBq) MBq)

reflux reflux

scan scan

transit transit

gland gland

for for

fluids fluids

bymouth bymouth

hours hours

Clear Clear

Gastro-oesophagea/ Gastro-oesophagea/

6 6 orally orally

Oesphaegeal Oesphaegeal

Nil Nil

Salivary Salivary

4 4 None None (cont'd)

Radiopharma- Route of Patient ceuticalls and Patient administration Quantitative preparation dose position and delay Equipment Technique analysis Comment Gastric emptying Nil bymouth 1 mCi (35 MBq) Standing, sit- Oral adminis- LFOVwith Continuous re- ROI over sto- This is a very for6 hours 111 In DTPA in tingor lying tration. No similar gamma cording of stomach contents, variable tech- 100 ml milk (depending delay camera with mach activity plot time activ- nique. It must (liquid meal); on stan- dual isotope re- anteriorly for ity curve and be standardized 1 mCi (35 MBq) dard- cording facility 60minutes. calculate log locally 99 mTc Iabelied ization) and high ener- Simultaneaus time and T 112 bran or chicken gy collimator. acquisition in emptying liver Iabelied in Computer dual isotope vivo (solid) mode

Duodeno-gastric bile reflux Nil by mouth 6 m!J.Ci (200 Supine I. V. injection LFOVgamma Following Displayimages for 6 hours MBq) 99mTc 99mTcHIDA. camera with HIDA injection corrected for HIDA. 500Ci No delay. Oral dual isotope 60 second eross-over (20 MBq) 111In mln-DTPAat • tecording anterior ab- activity. Using DTPA in fatty 30minutes facility and dominatim- ROimeasure meal afterHIDA high energy ages at 2, 5, 10, the amount of (20 minutes if collimator. 15, 20and30 99mTc-HIDA in post chole- Computer minutes. Give gastric area cystectomy) mln-DTPA outlined by fatty meal, rec- mln-DTPA ord 60 second images every 5 minutes for 60 minutes

Localization of G. I. bleeding None lOmCi (400 Supine I. V. injection. LFOVgamma Anterior ab- MBq) 99mTc Nodelay camera with dornen images Iabelied auto- GAPorhigh every 5min- logousred resolution utes for30 blood cells collimator minutes. Then as indicated up to24 hours lateral views as necessary Meckel's diverticulum 6 hours nil by 5mCi~200 Supine I. V. injection. LFOVgamma Anterior ab- N/A Pentagastrin mouth MBq) 9 mrc Nodelay camera dominalim- with or without pertechneta te ages every nasogastric suc- 5minutesup tion may also be to 30 minutes. used to enhance Lateral and ectopic uptake posterior im- while removing ages as indi- intragastric cated activity

Gastrointestinal blood loss measurement None 200 flCi (7 MBq) N/A I. V. Weil scintilla- Blood samples 51 Cr Iabelied tion counter, at 15 minutes, 7 autologous red !arge specimen and 14days. % administered dose blood cells. scintillation Faecal collec- mlofblood in faeces x 1000 Prepare stan- counter tion collected sample = dard solution and radioactiv- % litre administered ity measured dose over2week in blood period Large specimen scintillation counter makes the technique acceptable

Liver!spleen scan

None 4mCi ~150 Standingor I. V. injection, LFOVgamma Standard Usually none Maybecom- MBq) 9 mrc lying 15 minutes camera with 4views bined with 'first HSAcolloid delay GAPorhigh (A, P, RL, LL). pass' blood flow resolution 500 000 counts study collimator each with extra anterior view with costal margin marker

(cont'd over) (cont'd)

Radiopharma- Route of Patient ceuticalls and Patient administration Quantitative preparation dose position and delay Equipment Technique analysis Comment

Hepatobiliary scan 6 hours nil by SmCi ~200 Supine I. V. injection. LFOVgamma 400000 count Usually not Gallbladder mouth MBq) 9 mTc Nodelay camera with image of Ii ver done response to HIDAor high resolution anteriorly at cholecystokinin equivalent collimator 2 minutes. or fatty meal may Repeat for the bemeasured same time ev- after gall- ery 5 minutes bladder filling to 30 minutes. Rt lateral view after 30 mins. If gallbladder and duoden um are not visualized continue inter- mittently up to 4hours

Spleen scan None 1 mCi (40 MBq) Standingor I. V. injection, Standard or 250000 count Results plotted 99mTc Auto- lying 45minutes LFOVgamma imagesA, P, on paper taking logous dena- delay camera with LAO, LL, LPO 3 min as 100%. tured red blood GAPcolli- views. Blood Record time to cells mator. Stan- samples taken 50% activity dard weil at 3, 10, 20 and (normal9-18 counter 30minutes. minutes) Theseare haemolysed and2mlsam- ples measured

Bane marrow None 99mTc HSA Lying I. V. injection. LFOVgamma Sminuteim- Routinely none Do routine liver/ colloid 10 mCi 15-30 minutes camera with ages ofpos- spieen scan (370MBq) delay GAP collimator terior thoracic per 1.73 m 2 or whole body andlumbar body surface imaging device spine, posterior pelvis, both shoulders, both upper femora (distallimbs if indicated) lateral skull. Plasma volume Plasma volume None 10 [tCi f0.3 N/A I. V. Weil scintilla• 10 ml hepari• MBq) 1251 hu• tion counter nized blood vol injected (10) x CPM standard manserum sample before X dilution of standard albumin. injection. extrapolated CPM/1 ml plasma at Preparation of Administration timeO standard of 1251HSA. solution 10 ml heparin• Normal range ized blood sam• 30-40 ml kg- 1 ples at 10, 20, body weight. 30 minutes. Count1 ml plasmasam• ples and stan• dardfrom opposite to in• jection

Red cel/ mass Red cell volume = None 10 [tCi 10.3 N/A 16 ml ofla• Weil scintilla• Preinjection 10 WB std CPM/1 ml x MBq) 5 Cr belled blood tion counter ml heparinized dilution - plasma sodium chro• injected i. v. blood sample std CPM/1 ml x std matetagged with no extra• then samples plasmacrit WB to20mlof vasation. Re• 10, 20 minutes. CPM/1 ml - plasma patient's whole mainder used Wholeblood CPM/1 ml X blood for standard andplasma vol. injected x plasmacrit preparation samples are haematocrit counted Normal red cell volume: males 25-35 ml kg- 1; females 20-30 ml kg- 1; Total blood volume: males 55-80 ml kg- 1, females 50-75 ml kg-1

(cont'd over) (cont'd) Radiopharma• Route of Patient ceutical!s and Patient administration Quantitative preparation dose position and delay Equipment Technique analysis Comment

Red cell survival and sequestration

None 1.5 ~-tCi(0.05 Supine 16 ml injection Weil scintilla• Blood sample Plot blood sam• Normal value MBq) kg- 1 intravenously tion counter. takenat24 ple count rates 25-35days body weight of Collimated hours and then onsemilog 51 Cr sodium scintillation 3timeseach paperand chromate liletector weekfor3 estimate T112 • tagged to weeks. Counts Sequestra- 20m! blood are recorded tion results ex• over the pre• pressed as ratio cordium, of spleenand precordial to liverat the spleenand same times as spieen to liver blood samples ratio

B12 absorption (Schilling Test)

Fasting from 0.5 ~-tCi(0.02 N/A Oral Weil scintilla• Administer Measure Normal value midnight and 2 MBq) tion counter 57 Co B12, Inject radioactivity of 9% in 1st24 hours after oral 1 mg stable B12 a 5 ml aliquot hours, < 1% in vitamin B12 1-2 hours ofurineand 2nd 24 hours. If administration later. Collect standard. less than 6% ex• urine for 24 creted repeat hours twice. with intrinsic fac• Prepare a 57 Co tor. The two tests B12 standard can be combined with two differ• ent radioactive cobalt Iabels CPMin5mlof % in 24 hours = urine X urine vol/5 CPMin5mlof std X dilution factor x 100 Ferrokinetics None 5 t-tCi (0.2 MBq) N/A Intravenous in- Weil scintilla- Draw 6 ml sam- Ploton semi Normal T112 = 6- 59Fe citrate injection of 5 ml tion counter ple heparinized log paper de- 120 minutes. Red cubated with of Iabelied blood at 10, 30, termine T112 • cell incorpora- plasma (use plasma 60, 90 minutes tion = 60-80% of donor compat- after injection dosein 7-10 days ible blood) if from another Red cell mass the iron bind- vein and then and survival and ing capaci\Y is at 24 hours and sequestration <10gdl-. alternate days can be measured Prepare stan- for3 weeks simultaneously dard solution

% RBC incorporation of 59Fe per day CPM 5 cc blood x red cell mass/5 x 100% - CPM X 20 x decimal haematocrit Lymph node imaging None 1 mCi (50 MBq) Supine Subcutaneous LFOVgamma Image regional Usually none 99mTc HSA injection at site camera with Iymph nodes, micro colloid depending on GAPorhigh cover the injec- nodes tobe sensitivity tion site with examined. collimator lead if in field 2 hour delay ofview

67 Gallium whole body scan Mild purgation 50 t-tCi (1.85 Lying I. V. injection: LFOVgamma 200 000 count Possibly use Usually combine during course MBq)kg- 1 48 hour delay camera with 1, images. Views subtraction with liver/spleen of study body weight of (occasionally 2 or3 pulse to cover whole technique for scan 67Ga citrate 6 hours) height ana- body or local liver lesions Iysers and high areas as clini- energy cally appropri- collimator or ate. Repeat at wholebody 72hours imaging device White ce/llocalization study None 500 t-tCi (20 Supine Intravenous, 3 LFOVgamma Anterior and N/A MBq) mln- hoursand24 camera prefer- posterior views autologaus hours ably with dual of chestand oxine Iabelied PHA, with abdomen. Re- leucocytes highenergy cord images 5 collimator min each at 1 and 3 hr. Other views as clinically indicated. Repeatat24 hours for 7 min perview. APPENDIX TWO Risk factors and dosimetry A. B. Brill

A2.1 INTRODUCTION risk. We strive to conduct only needed proce• dures, i.e. those that could make a difference The practice of medicine, like many other dis• regarding choices of patient management. We ciplines, is inextricably involved with benefit-risk need to strive to have the best equipment and the decision making. This relates to actions taken or appropriate isotopes available to use in such cir• deferred in all areas of patient management, i.e. cumstances, and to choose the best combinations both diagnosis and therapy. Heightened radiation and doses to provide needed information (NCRP concerns now affect and could increasingly im• 70, 1982). A patientwho realizes thatcarefulatten• pact on the practice of radiation-related special• tion is being paid to these issues is likely to feel ties. Public concern derives in part from increas• reassured. When called upon to answer a pa• ing awareness of the fact that we live in an in• tient's specific risk-related question, one has a creasingly complex world in which obvious and unique opportunity to provide information to a subtle risks are a natural part of life) and also that person whose full attention you have. At such a many of these risks are increasing in both de• time, one has the greatest chance of getting veloped and developing nations. beyond superficial barriers and emotional biases Exposures to some of these risks have signifi• and maybe even allay some misplaced fears re• cant potential impact on human health. Medical garding radiation risk. In these discussions, it is radiations have a strong positive impact on sometimes useful to relate procedural exposures health. On the other hand, chemical toxins found to doses and risks from common generally in increasing amounts in food and human tissues accepted life circumstances. As practitioners we are likely to confer significant negative effects. need to be knowledgable concerning the risk for Whereas it is very easy to measure minuscule the average patient and for patients at unusual amounts of radiation, it is very difficult to measure risk, whether this be from their disease, from the organ contents of chemieals even when tissues are particular radiation exposure they will receive, or available for assay. The fear of things 'nuclear' from the anxiety that they may have. A know• arises in part from the mysterious non-touchable ledge of the base upon which current knowledge aspects of the atom and its forces, plus deep• rests is of importance for one' s confidence in the seated anxieties regarding nuclear weapons and reliability of current dogma, and also so that ex• the possibility of their use in war or terrorist acts. planations can be given in appropriate depth to Unfortunately, nuclear medicine, radioactive persons of differing backgrounds when such dis• waste disposal, nuclear power, and reactors in cussions arise. general, are alllumped together in many people' s The press is quick to pick up on and report minds. In nuclear medicine, doses administered issues relating to radiation health. Recent concern to patients usually exceed natural background by has focused on radon, and we need to learn several fold, and many patients ask questions enough about that issue to compare it to other concerning risks from our studies. Nuclear medi• potential exposures, including 133Xe, for example, cine staff members need to be well informed con• used in nuclear medicine. If possible, we should cerning these issues to answer these questions be able to discuss such issues in sufficient depth to correctly, andin such a way as to inspire patient win listener confidence of our expertise. The prob• confidence. lernthat arises isthat when such matters are first The choice and manner of conduct of pro• reported there is often too little information gener• cedures requires a balance between benefit and ally available. At that point we may not have the Dose assessrnent 607 needed Ievel of understanding of the issues in• accepts the whole-body radiation risk figures from volved, and if this is the case we should say so. the Japanese A-bomb survivors, those numbers National and international radiation protection (cancers per million per rem whole-body dose) bodies, and nuclear medicine, and health physics can be multiplied by the whole-body dose equiva• societies all have groups which focus on these lent (EDE), to estimate the fractionallifetime in• matters, and which can be called upon to answer crease in cancer risk to the individual. As one specific questions as they arise. Even when one develops data on internal exposures to chemicals, cannot answer a patient' s question immediately, a and the risk associated therewith, the risks from quick follow-up after obtaining the needed in• chemical exposures could be calculated and sum• formation may be very useful, and certainly more med with the propagated radiation risk data. so than a hastily given imprecise answer to a The increasing gap between natural back• thougHtful question. ground and nuclear medicine doses could be used The Ievel and variations in natural background to suggest that nuclear medicine procedural risks radiation in different places is often given as a are less than previously believed, relative to natu• reference point relative to potential risks of ral background. However, at the same time as specific procedures. Recent information and ~ub assessments of natural background point to an licity regarding the significant contribution 2 2Rn increase, evidence of an increasing cancer risk makes to individual radiation exposure has emerges from continued follow-up of the attracted great attention. Variations in local geo• Japanese A-bomb survivors. Recent studies from logy, water supply and home construction prac• Japan are consistent with a two- to threefold in• tices result in significant differences in radiation crease in low linear energy transfer (LET) risk exposure depending on specific factors which are coefficients (Sinclair, 1987). Thus, it appears that home and region specific, and hence the use of our previous assessment of the 'relative risk' of natural background as the reference for acceptable nuclear medicine procedures, i.e. relative to natu• dose Ievels is a less stable number than previously ral background radiation, is essentially un• realized. Recent revisions of accepted sea Ievel changed, based on changes in our understanding mid-latitude assessments of natural background, of both dose and risk coefficients. for example in the USA, places this at 300 mrem (NCRP 93, 1987), effective dose equivalent (EDE). A2.2 DOSE ASSESSMENT Note: the EDE weights the rem dose by a set of organ dose weighting factors to estimate the A2.2.1 GENERAL whole-body risk equivalent of partial body expo• sures. Naturalbackground was previously given Dose estimation involves the measurement of at 80 mrem dose equivalent (OE) for many regions absorbed dose received by tissues, and is ex• in the USA (NCRP 45, 1975). This four- to fivefold pressed in various units based upon energy increase in our estimate of the Ievel of natural deposited by the various primary and secondary background exposure does not suggest that natu• radiations. Macroscopic dosimetry provides esti• ral background is increasing, but that we now mates of average dose received in the different have new ways of computing dose, i.e. the effec• organs. The question often arises as to how a tive dose equivalent, which makes it possible to particular patient's condition will influence the add the radon lung dose to whole-body and par• dose, i.e. will the dose be more or less than tial-body dose from other contributions to natural average values for normal subjects? A second background dose, as discussed below. A discus• Ievel of uncertainty that complicates the sion of the notions underlying additivity of dose dosimetry of internal emitters arises from non• contributions is presented in Lam (1988). uniform spatial distribution, and the techniques Among the rationale for the development of the and data needed to calculate dose distribution at EDE notion was the need in occupational safety the cellular Ievel (microdosimetry) are not weil prograrpmes to calculate the integrated dose to established. Doses from radiopharmaceuticals workers exposed to various internal and external that accumulate intracellularly, and particularly doses during a working career. Further, the risk to those that accumulate inside the cell nucleus, are workers comes from radiation and chemical expo• significantly higher than predicted by 'macro'• sures, and in principle the EDE permits the in• dosimetry, i.e. average dose calculations. We tegration of risks from multiple sources. If one need to know more about the mechanisms of 608 Risk factors and dosirnetry carcinogenesis, and the nature of initiation and activity that concentrates in the organ plus dose promotion processes and radiosensitive sites, to from blood flowing through the organ. know how to compute and use microdosimetry The biological testing of a new radio• data for risk prediction analyses. An excellent pharmaceutical starts with animal studies. Small discussion of theoretical and practical aspects of animals, frequently mice, are given small doses, dosimetry, including microdosimetric consider• and the animal sacrificed at various times to obtain ations is presented in a two-volume series edited biodistribution data. The calculations of dose for by Kase et al. (1987). human studies take the mouse data, and scale the Great interest focuses on the use of increasingly activity measured in terms of fraction of the in• used new classes of intracellular tracers, including jected dose per organ to humans by adjusting for short-lived cyclotron-produced 11C, 13N and 150, weight differences. These preliminary dose esti• and such tracers as 111In-labelled white cells. This mates guide initial human trials in which direct has led to an increased need for dosimetry data, information on dosimetry and potential utility is and particularly for microdosimetry data from obtained from human studies. The hardest part of diagnostic studies. The recognition of the fact that dosimetry studies is the collection of good data short-range Auger electrons emitted during from human studies. The best studies employ radioactive decay can convey high radiation doses opposed detectors which are used to collect emis• to the radiosensitive cell nucleus, when incor• sion and transmission data from the various porated into DNA, suggests care in the use of high organs of interest, along with reference standards diagnostic doses, but supports consideration of for dose calibration. Multiple measurements are their potential utility in higher administered doses required over timesthat span at least two effective for radiotherapy. Because the margin between half-lives of the tracer. In addition to organ safe and effective doses is narrow in radiotherapy, counts, whole-body counter, blood and urine data careful attention needs tobe given to the measure• are needed. In the past, specialized equipment ment and assessment of radiation dose in these was needed, and relatively few institutions were circumstances. For diagnostic studies, electron in a position to collect and analyse such data. The emissions result in unwanted radiation dose, Situation is now different, and computer-based whereas they provide the rationale for therapeutic gamma cameras are capable of being used for such protocols. Choices affecting the design of such studies, and computer programs are now widely procedural combinations will be illustrated for available for use in the analyses. monoclonal antibody diagnosis and therapy. Tabulated dosimetry data almost always indi• cate the average dose to various organs based on studies done in normal volunteers. Little data are available for persans with abnormalities that may A2.2.2 MEASUREMENT OF MACROSCOPIC influence dose significantly (NCRP 70, 1982). The DOSE FROM INTERNAL EMITTERS greatest changes between dose received by nor• The calculation of radiation doses from internal mal and diseased subjects come when normal emitters requires data on the radioactivity dis• excretory channels are blocked. Thus, patients tribution following administration in the different with anuria receive higher doses (per unit admin• organs in which the material is distributed. The istered dose) from renal studies than do normal area under the activity-time curve (given in MBq h subjects. A similar situation applies to patients (!-!Ci h)) and referred to as the A tilda in the with biliary atresia, infiltrated administered notation used by the Medical Interna! Radiation doses, etc. There is a need to broaden the number Dose (MIRD) Committee of the SNM provides the of institutions doing careful dosimetry studies if first of the two pieces of information needed. The such data are to become available. Forthis reason, second is radionuclide-specific data (S factors in we will be more explicit on the methods that we MIRD notation) which is given in (cGy MBq-1 h have found most useful, and will illustrate this {rads !lCi-1 h}) for the different source organs using recently collected data on 111In-labelled anti• measured in terms of dose contribution to the bodies. various target organs in the body. For y-rays, the Aceurate standards, needed to calibrate in vivo source-target contributions to distant regions and in in vitro sample counts, are easily made by needs to be calculated, whereas for short-range weighing radioisotope-containing syringes before radiations absorbed dose comes only from the and after delivery of measured (i.e. counted) Dose assessment 609 amounts of radioactivity into tubes (for standard tients. Analyses are based on geometric means of preparation) and into the patient. One needs to the emission data from selected regions of interest avoid flushing syringes in these studies. Alterna• including organs, background sites and standards tively, one can count syringes before and after (Doherty et al., 1986). Other groups in many coun• delivery, but this requires carefully calibrated tries have used specialized counters to collect data systems to cover the wide range in activities for dosimetry of higher-energy nuclides than can accurately. The techniques for blood and urine be measured effectively with gamma cameras be• measurements are weil established in all nuclear cause of scanty side shielding and thin, low• medicine laboratories. The complete collection of efficiency crystals. urine and the measurement of urine losses is difficult to achieve. In many cases, where stool A2.2.3 DOSE ESTIMATES losses are negligible, or the time of measurements is short with respect to faecal excretion, whole• Organ doses for different radiopharmaceuticals body counts can be very useful. Since imaging are given in package inserts for all radio• studies require the administration of many micro• pharmaceuticals approved for use in humans. A curies, traditional whole-body counters are of lit• number of tabulations have been published which tle value, as they are too sensitive. Instead of a bring together these useful data. Doses are given traditional whole-body counter, we use an uncol• in absorbed dose ['er administered amount (Gy limated gamma camera, with the patient >5 m in Bq-1 or rads mCC administered). Since the qual• front of the detector, and count the patient, a ity factor for y- and high-energy ß-emitters is 1.0, standard, and room background for less than 1 these doses arealso equal to dose quivalent (cSv or min, to obtain retention data. Alternatively, any rem dose). reasonably good scintillation detector (high data The relative risk of X-ray and nuclear medicine rate capability) can be used for such studies. Initial studies has been presented in various ways. The measures at 15-30 min (counts in patientlstan• problern is complicated by different distributions dard) are used as the 100% reference against of dose and dose rate. A logical basis for summing which subsequent whole-body counts are com• the risks of partial body exposures and comparing pared. these to the risks of whole-body exposures was For organ activity determinations, a collimated needed, and several approaches, have been sug• gamma camera can be used which has been cali• gested. The International Council for Radiation brated for the particular low-energy y-emitting Protedion (ICRP, 1977) established a series of radionuclide under investigation. Calibration weighting factors to accomplish that task. These studies are accomplished by transmission and weighting factors are based on the relative con• emission imaging of a known activity source tribution of cancers of different organs to the total embedded in different amounts of scattering somatic risk based on whole-body exposures. material. Correction factors derived from such Thus, for example, if 15% of the cancer risk in studies are obtained and used with the measured women following whole-body exposures involves emission and transmission data sets from pa- the breast, then the weighting factor on breast

Table A2.1 Camparisan af dases fram lung studies/expasures Lung Effective Procedure Amount dose doseequiv. or nuclide administered (mrem) (mrem)

127Xep.a. lOmCi 47a 17' 133Xep.a. lOmCi no• 25b 222Rn p.a. Nat. background 2500d zooc ChestX-ray zoe 6e

• NCRP 70 (1982). bJohanssonetal. (1984). c NCRP 93 (1987). The lung dose comes from a-particles from radon daughters to the tracheal bronchial epithelium. ctBEIR (1988). The dose of 2500 mrem is to the tracheabronchial epithelium. • Kereiakes and Rosenstein (1980). 610 Risk factors and dosimetry dose would be 0.15. If a woman receives a 1 rem dose that killed 50% of the people exposed to breast exposure, this is assigned a whole-body A-bomb radiations in 30 days (the LD-5030) is dose equivalent of 0.150 cSv (mrem), which is variously reported as being in the range 155-350 denoted as the effective dose equivalent (EDE). In rads (Adelstein, 1987). The numerical value of the radionuclide studies which deliver dose to a series LD-50 that relates to medical practice, however, is of organs, the weighting factors are applied to quite different and many patients have survived these doses and summed to estimate the whole• deliberate doses of 1000 rads, whole-body, in body dose equivalent. Exposures to the gonads managed therapy situations, but at very signi• are also included and weighted in with somatic ficantly lower dose rates than from an A-bomb. risk, based on theoretical risk projections based on There is a significant difference between the out• animal studies (ICRP, 1977; NCRP 91, 1987). An come of accidental exposures and planned medic• example of the use of EDE in comparing doses al exposures for various reasons. The proper from environmental exposures and diagnostic choice of therapy depends critically on the lung studies is presented in Table A2.1. The EDE absorbed dose, and timing of treatment is of car• from environmental 222Rn is approximately ten dinal importance. Dose is well established and times higher than from the other tabulated expo• planned in radiotherapy and is almost never as sures, whereas, when considering lung doses well established early in the management of acci• alone, it is two to ten times higher than the refer• dents. Much has been written on this subject enced procedures tablulated. For detailed exam• (Hubner and Fry, 1980) which we will not repeat ples that illustrate the EDE computation, see ICRP here but will direct our attention to issues relating (1977). to radiotherapy with radionuclides.

A2.3 EFFECTS OF RADIATION: HIGH A2.3.2 RADIOTHERAPY CONSIDERATIONS DOSES (WANTED EFFECTS) (EXAMPLE FROM RADIOIMMUNOTHERAPY) A2.3.1 GENERAL Early investigators used 32P to treat poly• The effects of radiation therapy are wanted cythaemia vera (PV), and 131I to treat thyroid effects. In that situation our objective is to kill disorders (thyroid cancer and hyperthyroidism). cells, with the goal of killing abnormal cells, and The fact that high doses can be useful in treating preserving normal cells as much as possible. disease is now well established. It is also true that Effects of high doses of ionizing radiation have high doses can cause deleterious effects, such as been well known and well documented for many leukaemia in both PV and thyroid cancer patients years. This comes from occupational data (miners treated with high doses, but the benefit-risk ratio exposed to pitchblende, radium dial painters, and still favours the use of these therapies. A number accidents in the workplace), untoward effects in of targeting strategies have been attempted to patients receiving high-dose radiation therapy, achieve higher therapeutic concentrations in and more recently from the effects of A-bomb tumour tissues. Compounds that are strongly exposure in Japan. Early effects depend on the localized in tumour tissue are under intensive part of the body exposed, the kind and amount of search. 131I-meta-iodobenzylguanidine (MIBG) is radiation, and the rate at which it is administered. an example of one such compound being used for Following doses in the range of 50-100 rads or adrenal medullary tumour therapy (McEwan et higher whole-body dose, changes can be al., 1985). With the development of hybridoma observed in several body systems. Rapidly pro• technology, great impetus has been given to the liferating tissues show the greatest effects, since use of monoclonal antibodies for diagnosis and rapidly turning-over cell populations have a larger more impetus toward therapy. High tumour to probability of being in radiosensitive mitotic normal tissue ratios are required for successful stages than do resting cells. This accounts for the therapy, and at the sametime dose to the bone high radiosensitivity of haematopoeitic cells and marrow and other critical organs needs tobe kept gastrointestinallining cells. Some tumour cells fall at acceptable levels. into this same category, and for this reason there For many years there has been a recognition of has been a long history of efforts to target the need for better means of treating ovarian radionuclides to tumour tissue. The whole-body cancer, a radiosensitive common cancer, and we Late effects of radiation (unwanted effects) 611 will use this as an examrzle in our discussions. the treatment field. Ideally these would be iso• Isotope therapy with 2P-CrPO, and 198Au• lated cells, seeding the peritoneal cavity. If this is labelled colloid has been given intraperitoneally the case, then cell surface directed antihoclies with varying success in many clinical trials. Com• need to be tagged with an emitter whose radi• plications which arise in the course of these treat• ations penetrate on the order of one cell diameter, ments includes bowel necrosis, presumably due i.e. approximately 10 rtm (0.001 cm). Thus, using to high local doses from poorly distributed 90Y, the largest fraction of its ß-energy will deposit radionuclides, i.e. loculated injections, and mar• in the normal tissue to which the malignant cell is ginal success has been generally reported. Recent• juxtaposed. This can be to omenturn or bowel, ly, there has been increasing enthusiasm for the typically, in the peritoneal space, or in hone, to use of radiolabelled monoclonal antihoclies in which 90Y that breaks free from its antibody bind• treatment of this disease. Several antihoclies are ing site may attach, and which could pose a being used. In Britain, 90Y-labelled HMFG1, a hazard to hone marrow. If the tumour masses are monoclonal antibody targeted to ovarian cancer, larger, then the deep penetration by energetic is being used in clinical trials (Epenetos et al., ß-radiations would be needed to treat cells that are personal communication) .. In the USA, a feasi• distant from the site of attachment of the anti• bility study is now beginning, using a different body. Since one of the objectives in therapy is to ovarian cancer targeted antibody, intraperi• kill all tumour cells, and since it is unlikely that toneally injected 90Y-labelled OC-125(Hnatowich any antibody will target all cells, then a particle et al. ). The considerations that dictate the choice of whose range is greater than one cell diameter is radionuclide and antibody include the effective needed. half-life and emissions from the radionuclide, and A further problern that faces intraperitoneal antibody-related factors that influence the phar• therapy is that this route of administration deliv• macokinetics, both of which factors determine the ers material primarily to the surface of the tumour radiation dose distribution. It is generally believed cells. When they are isolated cells, that can be that a therapeutic nuclide should have a radio• effective. When tumour masses are larger, then it active half-life of the order of two to seven days. is important to get to the deep portians of the ldeally blood Ievels should be high, to provide a tumour as well, and two different approaches can driving force pushing tracer into the tumour, and be considered. The first was referred to above, non-target tissues should have low uptake and and that involves the use of energetic ß-emitters. retention. Excretion of the isotope should be slow, The other possibility that needs to be explored and should occur through the kidney, in the case involves the use of two different routes of of intraperitoneal therapy of ovarian cancer, to administration, i.e. intraperitoneal for surface minimize added dose to the gastrointestinal tract. targeting, and intravenous for delivery of dose to Radionuclidic considerations depend on the type deeper sites in the tumour. One could use the of tumour distribution and the size of the masses same nuclide, or a different one, whose properties tobe treated. The emissions should be particulate, are a better match to the kinetics and biodistribu• so as to deliver high dose over a short range, tion of the particular antibody to which it is ideally confined to the tumour volume. The maxi• attached. Clearly, dosimetry considerations will mum range of the 2.2 MeV ß-emissions from 90Y is play an important role in selection of appropriate 1.0 cm in tissue (average = 0.36 cm). The utility of combinations, and experience gained in animal 90Y for treatment depends on kinetics of the tracer, and human research studies will determine the target to background ratios, and geometry of the potential role of such combined approaches. target with respect to radiosensitive normal tis• sues. A2.4 LAIE EFFECTS OF RADIATION The primary treatment of ,ovarian cancer is (UNWANTED EFFECTS) surgery, along with traditional radiotherapy directed at the tumour area, including known A2.4.1 GENERAL local pathways of dissemination. Chemotherapy and radioimmunotherapy are directed at metas• The effects of radiation encountered in radiation tases which have evaded the surgeon and the therapy are wanted effects. In that situation our radiotherapist. The anticipated role of im• objective is to kill cells, with the goal of killing munotherapy is to find and kill cells that have left abnormal cells, and preserving normal cells as 612 Risk factors and dosimetry much as possible. In the discussion we are now radiation sensitivity, a phenomenon associated embarking upon, we focus on the late effects of with deficient radiation repair mechanisms (Pat• low doses of radiation, where these effects arenot terson et al., 1984). These observations provide what we are seeking to achieve but are unwanted direct confirmation of the existence of repair side effects. Since the objective of nuclear medical mechanisms in man. Fortunately, diseases involv• diagnostic procedures is to obtain clinically ing defective radiation repair mechanisms (such needed information with minimum risk to the as ataxia telangiectasia and xeroderma pigmento• patient, any late effect of the radiation we deliver sa) are sufficiently rare that it is not deemed neces• has tobe looked upon as unwanted. The infor• sary to make adjustments in population exposure mation we have on radiation effects of low doses guidelines (BEIR, 1980). However, when such of radiation is based on extrapolations down into persans come for radiation therapy, it is very the low-dose region from data obtained at high important that they be identified as individuals, as doses. Because of the uncertainty in making these they can be expected to sustain serious injury or extrapolations, we always state that our know• death from doses which are well tolerated by ledge in the low-dose region is imprecise. This 'normal' individuals. creates the impression in the general public that Information on the relation between dose and we do not know what is happening at those doses, subsequent expression of radiation-induced dis• and that there may be significant unexpected risk ease in humans relies heavily on findings from the from procedures which deliver low doses. That is follow-up of the Japanese A-bomb survivors. Un• misleading because, in fact, given present like most other human data, exposure to different radiobiology knowledge the larger concern in the doses of radiation in the survivors was not con• low-dose region is whether the risk is as high as founded with prior health status, age or sex, and extrapolated from high doses, or less. long-term follow-up has been achieved with un• It is generally conceded that there is. more precedented success. Additional support for the known about radiation risks than about any other findings from these studies comes from very simi• potentially deleterious agent. Extensive radiobiol• lar results derived from follow-up in the UK of the ogy information comes from a long series of care• effects of partial-body, fractionated, high-dose• ful animal and plant radiobiology studies con• rate radiation therapy of ankylosing spondylitis, a ducted over many years. The ability to separate disease affecting young males predominantly the importance of the different factors, i.e. dose, (Darby et al., 1984). radiation quality, doserate and other co-factors, Epidemiology studies are difficult and expen• can be assessed only in animal systems, and this sive to conduct, and require many years before has been done. Observations at high doses pro• conclusions can be reached. The strength of these vide data that are useful for interspecies compari• conclusions is often diminished by inherent sons at high doses. Knowledge of mechanisms of limitations in human research. A healthy worker radiation action is needed to provide insight into effect has been noted in some occupational expo• the expected rates at lower levels than can be sure studies where employment selection factors experimentally resolved. The results of animal can lead to underestimated risk of radiation with studies establish the principles upon which respect to the general population. Even in the human radiation data are assessed. The need for Japanese studies, where there should be mini• human data arises in order to facilitate scaling the mum bias, the question has been raised concern• results of animal studies to humans, and alsotobe ing the possibility that the 'weakest' persans sure that similar mechanisms operate. An exam• exposed had the highest probability of dying from ple of the latter is in the area of radiation repair early effects, and hence the surviving population mechanisms. In cell culture systems, radiation represents a healthier cohort than average. De• repair mechanisms have now been clearly demon• spite the various problems associated with the strated. In these processes, abnormal segments of Japanese A-bomb survivors study, it provides the DNA are excised and replaced with normal seg• besthuman radiation effects data, and represents ments. For many years theory has associated such the major source of information used by national processes with the shoulder region of ex• and international bodies responsible for radiation perimental dose-response curves. Now we know policy making. from studies on radiation repair mechanisms that there are animals and persons with heightened Late effects of radiation (unwanted effects) 613

A2.4.2 DOSE-RESPONSE CURVES model, and second, they based their calculations on the linear risk model, and failed to include a Statistically valid data on the effects of radiation in correction for the lower radiobiological hazard irradiated human subjects are available primarily from low dose rate radiations. These have been following high-dose, high-dose-rate exposures. documented extensively in animal and plant re• Analysis of effects at whole-body doses lower search and the effects of low dose rate radiations than 50 rads requires the extrapolation of data as from occupational, medical and environmental gained at higher doses into the low-dose region. radiations are believed to lie between 2 and 10 Various models have been used for this purpose. times less than from highdoserate radiations. As These can be classified in a number of ways. These they could not decide on a particular value forthat include linear, greater than linear, and less than correction factor, they ignored dose rate consid• linear models, and there is greatest radiobiological erations, and estimated the risk of whole body support for the less than linear models for low• radiation from low dose rate sources at 3-4 times dose predictions. No good human data have been higher than previously accepted. This has had a presented which justify the use of greater than large impact on public perception of risk, as the linear models. Based on extensive animal and issues are complex, and the public is ill-prepared plant data, the US NAS BEIR Committee (BEIR, to cope with details regarding such emotionally 1980) based its best estimates of low-dose low-LET charged matters. Regulatory agencies in many human radiation effects on a linear quadratic countries are in process of reevaluating exposure model. In that model, a linear dose component guidelines, and in view of the continuing debates adds to a quadratic component, with the latter concerning these values, we have not included becoming dominant in the high-dose region. Risk tabulations from that report in late editing of this predictions from this model were intermediate chapter just prior to publication. The interested between lower estimates from a quadratic model, reader is referred to the BEIR (1990) report for and higher estimates from a linear dose response further information concerning this controversial model, and all these estimates were tabulated. matter. The data were also presented based on absolute At low doses, it is generally accepted that the risk and relative risk models. The former assume limiting slope of somatic and genetic effect curves that radiation risks add to the baseline expectancy is linear in the low-dose region. However, for of disease, while relative risk models assume that some end-points, skin cancer, and effects that radiation increases risk in a multiplicative fashion. require darnage to multiple cells, a threshold is Thus, relative risk projections assume that chil• known to exist. Some data suggest that there may dren, for example, who have a given increment of be beneficial effects of radiation delivered at low cancer above expectancy for their age cohort will doses, the so-called hormesis effect, and this is continue to express that relative increase through• presumed to be due to Stimulation of immu• out life. Thus, when they achieve older ages in nological or other reparative processes. Such which spontaneaus rates of cancer are high, they effects are manifest by a dose-response curve will express rates which are a multiple thereof. which dips below the baseline spontaneaus risk Thus, relative risk models result in significantly values at low doses (Hickey et al., 1983). higher risk projections than do absolute risk At approximately 100 rads, linear and quadratic models. components are believed to be of approximately In 1990, the US NAS BEIR Comm. issued a new equal magnitude. This eross-over point is demon• report (BEIR, 1990) in which they projected strated in many radiobiology experiments approx. 4 fold higher risk from low level ionizing (Brown, 1977), but there are little data in humans radiation exposures than previously considered. in which this value can be established. The one These were based on continued follow up of circumstance for which this can be justified is in Japanese A-bomb survivors, and reflected the Japanese leukaemia data, as reviewed in BEIR changes in dosimetry, which are still being de• (1980). The strengthofsuch analyses rests on the bated, and additional cancer mortality in the years extensive experimental radiobiology data cited since the 1980 report. Two decisions by that com• above, rather than on the statistical robustness of mittee account for the major change in their esti• the human data. At higher doses, all models, mate of the risk, and these are the use of the including the linear quadratic, need to include a relative risk model, instead of the absolute risk saturation term, i.e. where additional doses are 614 Risk factors and dosimetry associated with decreasing effect rates, due to the (b) Use of risk coefficients to estimate phenomenon of 'wasted radiation', i.eo a fraction probability of causation already of the extra radiation kills or transforms ~he ~bove-ref~r~nce? data describe the prospec• damaged cells 0 hvoeonsk of rad1ahon-mduced effects, ioeo the prob• abihty that an eoff~ct will be observed following whole-body rad1ation exposureso An alternative A.2.4o3 RADIATION RISK COEFFICIENTS means of encoding this information attempting to (a) Data relate observed illness to antecedent radiation ex• posures was developed in the USA in response to There are extensive data on somatic risks of radi• the need for data that could be used in courts of ation in human subjectso Much of it comes from law to adjudicate radiation injury caseso This was the studies on the Japanese A-bomb survivors, motivated largely in response to attempts by per• but an appreciable amount of data are available sons living in southern Utah near the Nevada from the review of data on persons who received weapons test site to recover damages they attri• radiation therapyo There are no good human data buted to radiation injuryo The NIH was instructed relating radiation exposure to genetic riskso The to develop tables that would relate the increased data collected on the A-bomb survivors extensive probability of malignant disease that had super• have not demonstrated a significant increase in vene~ with respect to estimated exposure dose, genetic effects following high-dose-rate whole• for d1ffer~nt ~ypes of cancer, and different ages, doses which in the heavily exposed aver• body sex and time mtervals since irradiationo The attri• aged greater than 25 radso Thus, projections of but~ble risk or probability of causation (PC) they hu~an genetic risk are based entirely upon ex• defmed was based on the notion that radiation penmental cell and animal radiobiology datao adds linearly to the natural risk (NR), and that based on analysis of the Japanese data, However, percentage increment is tabulated as the PC plausibility con• a~d st~tistical and radiobiology (NAS, 1984; NIH 85)o siderahons, the low-LET low-dose-rate doubling dose for genetic effects is estimated at approx• Probability of causation (PC) = imately 480 rads (SchuH et al., 1987)0 [Radiation risk (RR) + (RR + NR)] x 100 Risk coefficients for somatic effects based on Given a 30-year-old male exposed to 10 rads in 1980 from Japan were in close data available whole-body low-LET radiation, who at age 40 with the ankylosing spondylitis data, agreement develops leukaemia, the tabulated PC is 26% 0 and data from other human experienceo Data Examples for other malignancies, given the same in BEIR (1980) were recalculated by presenteod age/latency and dose, include the following: J~hn B01ce for an NCRP Committee Report for different tumours for different age groups, and TUMOUR PC (o/o) these appear in Table A202 (presented in Sinclair, Bone 81 1987)0 Oesophagus 0083

Table A2o2 Risk of fatal cancer Age Total Risk (years) Leukaemia Lung Breast Thyroid cancers (X10/Sv)

Male 25 1.72 6015 0032 1909 200 35 1.88 4030 0022 1200 1.2 45 2000 3013 Oo14 902 Oo9 55 1.83 2018 0008 705 008 Fernale 25 1.07 4080 8014 0057 2903 209 35 1.24 4o19 3o32 Oo44 1700 1.7 45 1.46 3073 0081 0031 11.9 1.2 55 1.45 2092 Oo35 Oo20 909 1.0

Note: Fatal cases per 1000 persans after 0.1 Gy per year for ten years (1 Gy). From Sindair (1987). Late effects of radiation (unwanted effects) 615

Stomach 2.8 tumours as indicators of prior radiation exposure Colon 0.83 at different ages from low-LET exposures. This Li ver 8.4 type of detailed information is not available in the Pancreas 1.9 usual tabulations of specific types of cancer Lung 3.8 Non-smokers observed following radiation exposure. 0.35 Smokers Epidemiological studies which allege radiation as Breast 2.6 (female) the cause of injury should be cast in doubt if based Kidney 0.69 on enhanced occurrence of low-probability can• Thyroid 11 cers in the presence of a diminished frequency of higher-probability cancers in the appropriate age, The above numbers are very high with respect to sex, dose and latent periods. the numbers of cases of a disease predicted a priori, i.e. at the time of radiation exposure. For (c) Changing values of risk coefficients example, the lifetime increment in risk of Risk coefficients for various solid tumours are in leukaemia following a 10 rad whole-body expo• the process of being adjusted upward, probably sure is approximately 2-4 x 10-4 (Sinclair, 1987). by factors of two to three. This is based on con• This is far less than the 26% number cited as the tinuing follow-up of the A-bomb survivors which PC. The reason for the discrepancy isthat the PC is now showing an increasing incidence of starts from the fact that the person has leukaemia, tumours in survivors who were in the younger or some other specific radiation-relatable disease, age groups at time of exposure. Increased risk and looks backward in time to estimate the rela• apparently awaited these individuals growing tive contribution of radiation versus all other into the age groups at which those tumours are causes lumped together (the spontaneaus risk). most frequently seen (Preston and Pierce, 1987). This assumes that the individual is comparable to The second reason for the increase is that there the 'general population', although in one tabu• have been adjustments in the estimated radiation lated case special attention is given to cigarette dose yields from the bombs, and the propagation smoking as a potent identifiable predictor. of radiation as a function of distance. Further, it It is clear that caution has tobe used in interpret• was previously believed that neutrons accounted ing the above numbers. The fact that the PC is less for more of the Hiroshima exposures than is now in smokers than in non-smokers is not because believed, and hence the weighting factors on the radiation is less hazardous to smokers, but be• y-radiations has increased to account for the cause their spontaneaus risk is much higher, leav• observed cancer incidence/mortality (Preston and ing less of a contribution for radiation. The hope Pierce, 1987; Science, 1987). had been that courts would be guided by these The third factor that has received attention in tables in adjudicating accidental and occupational the discussions regarding revisions of risk factors exposures. It was expected that the 'more likely is the increasing availability of incidence data from than not' notion would have been used by courts, the A-bomb survivor studies. Since at least 50% of and PCs greater than 50% attributed to radiation, cancers are cured by modern medical therapy, it is and those at lesser levels would have been dis• clear that incidence rates are two times higher counted. However, to date, the tabulated data than mortality. Only in recent years have cancer have been used quixotically in the US. In one registries been incorporated effectively into the notable case in California, darnage was awarded A-bomb survivors follow-up studies. Thus, an to a patient with Iymphoma following a low-dose increase in cancer risk coefficien ts w hich are based occupational exposure with a PC less than 1%. on incidence is a computational restatement of The court based its decision on the belief that the risk, and not a true increase in disease rates. exposure, small as it was, had increased the prob• Radiation-induced thyroid cancer is one of the ability of cancer, and since no other cause could be more commonly induced cancers, usually papil• identified it was assumed to be radiation related, lary, a type that is rarely fatal. Thus, thyroid and damages were awarded (Shaffer, 1985). cancer appears in incidence statistics, but not in Whether PCs are useful for their intended pur• mortality data, and therefore the switch from pose remains to be demonstrated. Nonetheless, mortality to incidence inherently would lead to an the tabulations do provide an excellent source of increase of greater than two in risk coefficients data on the relative sensitivity of different based on incidence data. 616 Risk factors and dosimetry

Lastly, lifetime risk projections require a com• perception. Among these are whether it is a risk to pleted follow-up for all individuals from birth to you as an individual, whether you anticipate a death. Since only 45 years have elapsed since the direct benefit, and whether it is risk which you August 1945 A-bomb explosions in Hiroshima accept voluntarily. Another is whether you and Nagasaki, the youngest exposed persons understand and believe the magnitude of the risk have a nurober of years left to live, before their as told to you. Third, you may accept the benefit of pattern of mortality will be known with certainty. the particular exposure or circumstance leading to In the case of leukaemia, the expression of in• it, but be fearful of related processes, such as an creased risk was no Ionger evident after 1970, 25 association of things 'nuclear' with the threat of years following exposure. For other conditions, nuclear war or terrorist actions. It is not surprising beside bone cancer, the period of increased risk that there is a widespread distrust of radiation, has not yet been completed and for some solid despite the many good things it affords. tumours the risk appears to increase in proportion Numerous sources document numerical com• to the natural risk observed at a given age (relative parisons between the risks of ionizing radiation risk model). As the population ages, one then and other life circumstances. A medical perspec• projects a continuing increase in radiation effect tive is presented in Brill (1985), and the nuclear with time and this risk projection modelleads to scientist perspective is documented in a book the highest estimated risk for this population (i.e. focusing on risk perception with respect to nu• a 15-fold increase for some cancers according to clear power (Cohen, 1983). Table A2.3 presents a Preston and Pierce, 1987). listing of different life circumstances which carry a Nonetheless, given the pattern of changes one in a million risk. Present data suggest that noted above, the National Radiation Protection these risks are equal to the increase in cancer Board (NRPB) in the UK now advocates revising mortality risk during a lifetime following a single occupational dose standards downward by a fac• 10 mrem whole-body exposure. tor of three, i.e. from 5 rem to 1.5 rem per year Shortening of lifespan is an easily understood (Science, 1987). It is a matter of history that radia• tion protection standards have been lowered se• Table. A2.3 One-in-a-million risks quentially over the years, not because of increased knowledge of radiation risk but because it was Risk Nature possible to do the same work with lower dose to workers, without unduly restricting the availabil• Existence Male, age 60 20min CVD•cancer ity or quality of needed procedures (or societal inNewYork 2days Airpollution benefits). The interpretation of the meaning of in Denver 2months Cosmic radiation maximum permissible dose has also undergone in stone 2months Natural recent revision. In the past, this was assumed to building radioactivity Miami water 1 year Carcinogens be an acceptable dose limit, whereas now it is NearPVC 10 years Carcinogens taken as the upper limit of acceptable dose, and plant one is encouraged to strive to keep doses as low as Travel reasonably achievable (ALARA). Canoe 6min Accident Bicycle lümiles Accident Car 300 miles Accident A2.5 RISK AND PERCEPTION OF RISK Airline lOOOmiles Accident 6000miles Cosmic radiation The risk of exposure to ionizing radiation has been Airline assessed in a systematic way by scientists and Work Coalmine lh Blacklung physicians in intensive and extensive fun• Coalmine 3h Accident damental and applied research. More is known Tyfaical lüdays Accident about radiation and its risks than any other agent actory known to impact on human health. Nonetheless, Miscellaneous given the opportunity to rank the hazards of Cigarettes 1.4 CVD•cancer radiation and other life circumstances, the aver• Wine 500ml Cirrhosis age person greatly overestimates the risk of Diet soda 30 cans Carcinogens ionizing radiations. a Cardiovascular disease. Many factors are likely tobe responsible for risk From Brill (1985). Summary 617

Table A2.4 Lifespan shortening associated with low-event probabilities are hard to rank against varying conditions better-known phenomena, and this no doubt in• Condition Days fluences public fears. Statistical analyses, including factor analysis, Unmarried (male) 3500 have been applied to the risk perception problern Cigarette smoking (male) 2250 and two factors were identified by Slovic (1987). Heart disease 2100 He graphed and labelled the 30% overweight 1300 first factor, dread Cancer 980 risk, defined at its high end (right side) by such Stroke 700 expressions as lack of controllability, the dreadful• Motor vehicle accidents 207 ness of the event, the extent of its impact, and the Alcohol (US average) 130 inequitable distribution of risks and benefits Accidents in home 95 Averagejob (accidents) 74 (Figure A2.1). Nuclear weapons and nuclear pow• Drowning 41 er score highest on the characteristics that make Job with radiation exposure 40 up this factor. Factor 2 is plotted on the y axis, Illicit drugs (US average) 18 labelled as unknown risk, and at the high end lie Naturalradiation (Beir, 1972) 8 hazards judged as unknown, unobservable, new, Medical X-rays 6 Dietdrinks 2 and delayed manifestations ofharm. Smoking as a Reactor accidents (UCS, 1977) 2a cause of disease lies at the centre of the diagram, Reactor accidents (Wash-1400, 1975) o.oz· as do the well-known hazards of Pb, Hg, DDT and Smoke alarm in home -10 coal exhausts. The largest concerns focus on the Airbags in car -50 issues at the right end of the factor 1 scale, and •rhese items assume that all US power is nuclear. UCS is Union appear to be independent of factor 2. This in• of Concerned Scientists, the mostprominent group of nuclear cludes various nuclear-associated activities, along critics. From Brill (1985). with nerve gas accidents, coal and uranium min• ing. The size of the dot encodes the attitudes toward regulation of each of the hazards. The concept, and Table A2.4 presents a ranked listing larger the dot, the greater the desire for strict of various conditions associated with lifespan regulation to reduce risk. Again, radiation• shortening. There is a wide divergence (4000-fold associated phenomena receive the greatest con• difference) between the risks of cigarette cern. It is instructive to rank the cost of increased smoking, and average annual medical radiation regulation per projected life saved in each cir• exposures (53 mrem per year). Accidents (motor cumstance. At present, the US Nuclear Regula• vehicles, accidents in the home and in the work• tory Committee requires the expenditure of place) are far rnore hazardous than rnedical diag• approxirnately 5 rnillion dollars per life saved from nostic radiation procedures, and the normal low-level radioactive waste disposal, site design operations of nuclear power plants (including and management, whereas it is difficult to find nuclear waste disposal). Accidents do occur, and societal approval for rnore than 10 000-100 000 the accidents at TMI and Chernobyl have severely dollars for medical therapies (renal dialysis or impacted on public attitudes toward nuclear pow• renovascular hypertension screening) or safety er. The accident at Bhopal once again reminds us appliances (auto seat bags). of the risks of accidents in non-nuclear areas, in this case involving chemicals. Such exposure can A2.6 SUMMARY come from production plants, uses in agriculture and food processing, and waste disposal. The Radiation doses from diagnostic nuclear medicine magnitude and severity of the health effects of the procedures have decreased in recent years be• Bhopal accident have been compared to the effects cause of the increasing use of short-lived low• of the Hiroshima A-bomb (Kurzman, 1987). The energy y-emitting tracers. At the same time, hazard of carcinogens from living for ten years increased use of tracers which enter into the near a PVC plant was cited in Table A2.3 as a one intracellular space raises questions concerning the in a million risk. It is not clear that this number is microscopic distribution of dose, particularly greatly different from the Bhopal type of disaster, when tracers with significant Auger emissions, which makes one uneasy about the magnitude of like 111In, 1251 or 201Tl are used. Additional in• such probability assignments. Large effects and formation on mechanisms of carcinogenesis will Factor 2 Unknown risk

LaetrileO 0 DNA Technology Hexachlorophene Mlcrowave ovensO Electrlc Fields Water Fluoridati~no Nitrites 0 0SST SaccharinO 0 O 0DES Water Chlori.nation~ O Goal Tar Hairdyes U t'olyvinyl Chloride Nitrogen Fertillzers Radloactlve Waste 0 Cadmium Usage 0 Oral Contraceptives 0 0 Nuclear Reactor Accidents Valium 0 Diagnostic X Rays M' ~ 02,4,5-T lrex Tricholoethylene Darvono 0 lUD Antiboitics O 0 0 0.. O Uranium Mining Rubber MfgO 0 Pestleides PCB' Asbestos lnsulation s 0 0 ODDT 0 Sateilite Crashes Nuclear Weapons Fallout o Gaffeine Auto Lead 0 Mercury o Fossil Fuels o Aspirin Vaccines 0 Lead Paint Factor 1 0 0 Goal Burning (Pollution) Dread risk Skateboards Ü()Auto Smoking (Disease) Exhaust (CO) 0 Nerve Gas Accidents D-CON LNG Storage and Transport Power Mowers o 0 0 SnowmobilesO Goal Mining (Disease) Trampolines o o Tractors 0 Large Doms AlcohoiO 0 Skyscraper Fires Electrlc Wir and Appl (Firesf Chainsaws Nuclear Weapons (War) 0 Horne Swimmlng Poolso d OEievators Underwater Const 0 Rec Boating 0 o Osmoklng (Fires) oSport Parachutes 0 Goal Mining Accidents Downhili Skilng 0 0 General Aviation Bicycleso / Motorcycleso 0 High Construction Electric Wir and Appl (Shock) BrldgesO Alcohol 0Railroad Colllsions FireworksO Accidents 0 Comm Aviation 0 Auto Raclng Auto Accldents

0 0Handguns Dynamlte

Factor 2 NOT OBSERVABLE UNKNOWN TO THOSE EXPOSED EFFECT DELAYED NEW RISK CONTROLLABLE RISKS UNKNOWN TO SCIENCE UNCONTROLLABLE NOT DREAD DREAD NOT GLOBAL CATASTROPHIC GLOBAL CATASTROPHIC CONSEQUENCES NOT FATAL CONSEQUENCES EQUITABLE NOT EQUITABLE INDIVIDUAL CATASTROPHIC Factor 1 LOW RISK TO FUTURE HIGH RISK TO FUTURE GENERATIONS GENERATIONS EASILY REDUCED NOT EASILY REDUCED RISK DECREASING RISK INCREASING VOLÜNTARY OBSERVABLE INVOLUNTARY KNOWN TO THOSE EXPOSED EFFECT IMMEDIATE OLD RISK RISKS KNOWN TO SCIENCE

Figure A2.1 Location of 81 hazards on factors 1 and 2, based on the relationships among 18 risk characteristics. Each factor is made up of a combination of characteristics, as indicated in the lower diagram. The !arger the circle, the greater the desire for strict regulation to reduce risk. (Modified from Slovic, 1987.) References 619 be needed before risks of these procedures are magnetic resonance imaging systems was mo• likely to be understood. It is well recognized that tivated by the desire to avoid public mis• the benefits derived from the administration of understanding about the word 'nuclear' if it were tracers in clinical nuclear medicine are far greater associated with the process. In retrospect, the than the theoretical risks associated with the low inclusion of 'nuclear' in MRI designations would doses used in diagnostic studies. Nonetheless, have afforded an opportunity to educate the pub• increasing estimates of radiation hazard are cer• lic to better understand the nature of such phe• tain to be followed by heightened concern on the nomena. Such an opportunity could have been part of patients and regulatory agencies. It is used to convey the minuscule or negligible risk important to realize that the increase in risk pro• associated with nuclear magnetic resonance, jections, based on linear extrapolations from A• where the risk is from the magnetic and/or radio• bomb exposure data, fail to account for the big frequency fields rather than from ionizing nuclear difference in dose rates, and that data are entirely emissions, which are not part of the magnetic lacking following low doses, such as received resonance process. from diagnostic medical radiation procedures. Further, the major factor responsible for the in• crease in risk coefficients is not the new REFERENCES dosimetry, but is the high future risk projected for Adelstein, S. J. (1987) Uncertainty and relative risks of the youngest A-bomb survivors. If these projec• radiation exposure. JAMA, 258, 655-7. BEIR (1980) The Effects on Populations of Exposure of Low tions turn out to be valid, then our long• Levels of Ionizing Radiation, National Academy Press, established policies in medicine of minimizing Washington DC. radiation exposures to children will prove to have BEIR (1988) Health Risks of Radon and Other Internally been prudent, and exposures delivered to the Deposited Alpha-Emitters, National Academy Press, general population which involve significant Washington DC. BEIR (1990) Health Effects or Exposure to Low Levels of exposures to children will have to be recon• Ionizing Radiation. BEIR V, National Academy Press, sidered. Washington DC. In any case, continuing effort needs to be de• Brill, A. B. (ed.) (1985) Low-Level Radiation Effects: A Fact voted toward the development of better targeting Book, SNM Press, New York. Brown, J. M. (1977) The shape of the dose-response strategies to increase the target-to-background curve for radiation carcinogenesis: extrapolation to ratios to increase the quality of diagnostic judge• low doses. Radiat. Res., 71, 34-50. ments and to improve therapeutic results as weil. Cohen, B. L. (1983) Before It's Tao Late: A Scientists's Case This will include the development of new chemi• for Nuclear Energy. Plenum Press, New York. cal compounds that enter into tissue-specific Darby, S. C. Nakashima, E. and Kato, H. (1984) A parallel analysis of cancer mortality among atomic metabolic processes, improved tumour-specific bomb survivors and patients with ankylosing spon• monoclonal antihoclies for improved diagnosis, dylitis given X-ray therapy. RERF Technical Report, TR and even more so for successful therapy, along 4-84. with improvements in instrumentation, image Doherty, P., Schwinger, R., King, M. and Gionet, M. (1986) Distribution and dosimetry of In-111 Labeled analysis techniques, and diagnostic decision F(ab'h fragments in humans In Fourth International strategies that utilize available information Radiopharmaceutical Dosimetry Symposium: Dosimetry optimally. for Ultrashort-lived Radionuclides, Radiolabeled Blood Moreinformation concerning the mechanism of Cells, Monoclonal Antibodies, Positron Emitters, Micro• radiation effects and repair is needed. This is dosimetry, Children, Fetus, Oak Ridge, Nov. 5-8, 1985, CONF-851113, ORAU, pp. 464-76. primarily motivated by the hope that if one under• Epenetos, A. A. et al. (personal communication) stands how radiation acts as a carcinogen we will Hammersmith Hospital, London. then know how other carcinogens work, and be Hickey, R. J., Bowers, E. E. and Clelland, R. C. (1983) able to block the process at early stages by Radiation hormesis, public health and public policy. Health Phys., 44, 207-19. appropriate therapy. Along the way we will need Hnatowich, D. et al. University of Massachusetts to obtain better information on dosimetry of Medical Center, Worcester, MA. agents we use, at the macroscopic and micro• Hubner, K. F. and Fry, S. A. (1980) The Medical Basis for scopic Ievels. Radiation Accident Preparedness, Elsevier/North• Public perception of risk now focuses on nu• Holland, Amsterdam. ICRP (1977) Recommendations of the International Com• clear power and other nuclear-related activities. mission on Radiation Protection, Publication 26. The deletion of the term 'nuclear' from nuclear Johansson, L., Mattson, S. and Nosslin, B. (personal 620 Absorbed radiation in patients

communication) Effective dose equivalent from NCRP 93 (1987) Ionizing Radiation Exposure of the Popu• radiopharmaceuticals. lation of the United States. Kase, K. R., Bjarngard, B. E. and Attix, F. H. (eds) (1987) NIH 85. Report of the National Institutes of Health. Ad Hoc The Dosimetry of lonizing Radiations, Academic Press, Warking Group to Develop Radioepidemiological Tables. London. NIH Publication No. 85-2748. Kereiakes, J. G. and Rosenstein, M. (1980) Handbook of Patterson, M. C. Bech-Hansen, N. T., Smith, P. J. and Radiation Doses in Nuclear Medicine and Diagnostic X• Mulvihill, J. J. (1984) in Radiation Carcinogenesis: ray. CRC Press, Epidemiology and Biological Significance (eds J. D. Boice Kurzman, D. (1987) A Killing Wind: Inside Union Carbide Jr andJ. F. Fraumeni, Jr) Raven Press. New York. and the Bhopal Catastrophy, McGraw Hili, New York. Preston, D. L. and Pierce, D. A. (1976) The Effect of Lam, G. K. Y. (1988) On the general validity of linear Changes in Dosimetry on Cancer Mortality Risk Estimates summation of dose equivalents for mixed radiation. in the Atomic Bomb Survivors, RERF Technical Report, Health Phys., 54, 57-61. TR 9-87. McEwan, A. J., Shapiro, B., Sisson, J. C. et al. (1985) Regan, J. D. and Setlow, R. B. (1976) in Biology of Radio-iodobenzylguanidine for the scintigraphic Radiation Carcinogenesis (eds J. M. Yuhas and J. D. location and therapy of adrenergic tumors. Sem. Nucl. Regan), Raven Press, New York. Med., 15, 132-53. RERF (1987) US-Japan Joint Reassessment of Atomic Bomb MIRD. Medical Interna! Radiation Dose Committee, Radiation Dosimetry in Hiroshima and Nagasaki, Final Society of Nuclear Medicine. (Publishes data on Report, 1987, available from RERF Office, NRC, decay scheme for tracers used in nuclear medicine, Washington DC. tables of computational factors needed for dose ana• Schul!, W. J., Otake, M. and Neel, J. V. (1987) A lyses, guidance on accepted analytic methodology, Reappraisal of the Genetic Effects of the Atomic Bombs. and periodic reports of dosimetry analyses for par• Summary ofa 34 year Study, RERF Technical Report, TR ticular radiopharmaceuticals.) 7-81. NAS (1984) Assigned Share for Radiation as a Cause of Science (1987) 236, 1649-51. Cancer. Review of Radioepidemiologie Tables Assigning Science Radiation Limits, News and Comment (1987) 236, Probabilities of Causation. Oversight on Radio• 1349. epidemiologie Tables, National Academy of Seiences Shaffer, W. G. (1985) Law review: Ietter to editor. Health Press. Phys. NCRP 45 (1975) Natural Background in the United States. Sinclair, W. (1987) Risk, research, and radiation protec• NCRP 70 (1982) Nuclear Medicine: Factars Influencing the tion: Failla memoriallecture. Radiat. Res., 112, 191- Choice and Use of Radionuclides in Diagnosis and Therapy. 216. NCRP 91 (1987) Recommendations on Limits For Exposure to Slovic, P. (1987) Perception ofrisk. Science, 236, 280-5. Ionizing Radiation.

Absorbed radiation in patients: a memorandum for the ethical committee

K. E. Britton

A2. 7 INTRODUCTION which is the same risk as smoking one and a half cigarettes in a lifetime or drinking half a litre of Radiationisanatural phenomenon. The current wine in a life time, or indeed that risk of death for a method of measuring absorbed radiation is the man aged 42 living for a day or a man aged 60 effective dose equivalent in units called milli• living for 20 min (Brill, 1985). sieverts (mSv). This allows different types of radiation from different sources, X-rays, y-rays, cosmic rays etc., to be compared. Normal ex• A2.8 PERCEPTION OF RISK posure in London is about 0.15 mSv per month, including that from our bodies. The computed The popular perception of radiation risk is much risk of death from 0.1 mSv is one in a million greater than in fact it is. Studies in the USA of Consent forms 621 league of women voters and college students put statement that only if a risk was greater than 1 in the risk of nuclear power first and business and 2000 was it a risk worth worrying about and professional club members put. the ris~ at eighth radiation risks are much below this level (Table of a list of 30 agents, whereas m fact lt was 20th A2.5). (the risk was 1500 times less than average cigarette smoking, 1000 times less than average alcohol consumption, 500 times less than motor vehicle A2.10 PREGNANCY AND RADIATION driving, 30 times less than swimming and 1.0 times The radiation sensitivity of the fertilized ovum is less than bicycling (Brill, 1985). The hfespan of the same order as that of the unfertilized ovum, shortening on a population basis associated with so that the so-called ten-day rule (that studies of medical X-rays is 6 days, of which the nuclear the lower abdomen involving the use of X-rays medicine contribution is 4 h, as compared with: should be limited to the first ten days after the natural background radiation 8 days; accidents in start of the last menstrual period) was never the home 95 days; accidents at work 74 days; heart radiobiologically sound (Mole, 1987) and not disease 2100 days as examples (Brill, 1990). directly applicable to nuclear medicine pro• cedures (Longmead et al., 1983). A2.9 ICRP Women of child-bearing age who are pregnant are most sensitive to radiation during the period The International Commission on Radiation Pro• of fetal organogenesis between seven and 17 tection (ICRP) has defined annual limits for the weeks of pregnancy, at which time most women absorbed radiation to be received by various know that they are pregnant. No pregnant pa• populations (ICRP, 1977/8). The level of exposure tients should be considered for a research study for pregnant women should be less than 0.5 mSv, and any patient who was uncertain as to whether for members of the public less than 5 mSv (and or not she was pregnant should not normally be preferably no more than 1 mSv) and for occu• considered for a research study involving the di• pationally exposed workers less than 50 mSv agnostic use of radiation. However, the effective (natural background is 1.87 mSv per year). Typical dose equivalent of 0.5 mSv absorbed radiation in diagnostic studies and their effective dose equiva• any women of reproductive age who turned out lents are given in Table A2.5 (Shrimpton and Wall, subsequently to be pregnant would give a 1: 1986; DHSS, 1988; Sheilds et al., 1987). 100 000 risk of darnage to the fetus and 5 mSv a It is normal nuclear medicine practice to relate 1:10 000 risk as compared to the current risk of the absorbed radiation dose from the nuclear congenital abnormality in a delivered baby of ab• medicine procedure to that of the same organ out 1:40. The legal requirements set out in the undergoing an X-ray procedure, partly because Ionising Radiations Regulations 1987 is that the many patients are familiar with X-ray studies of dose limit for the abdomen of a women of repro• the organ about which they are concerned and ductive capacity 'shall be 13 mSv in any consecu• partly because it serves as a familiar frame of tive three-month interval', and for the abdomen of reference to the referring clinician. It is usually not a pregnant women 'shall be 10 mSv during the appropriate to relate absorbed radiation dose to declared term of pregnancy' (Ionising Radiation that of a ehest X-ray since for a ehest X-ray, de• Regulations, 1987). pending upon the machinery used, it varies from 0.01 to 0.1 mSv. The risks from the injection of contrast media A2.11 CONSENT FORMS and radiopharmaceuticals are shown in Table A2.6. It can be seen that the risks from the radia• It is proposed that for investigations involving an tion involved for diagnostic X-ray and nuclear absorbed radiation dose of less than 5 mSv the medicine studies are much less than those from phrase in consent form is: the pharmaceutical preparation itself. Given this information, the question is how to get over the The study involves administration of (X-rays) (a very low risk associated with diagnostic X-ray and tiny amount of radioactivity) at a level con• nuclear medicine procedures to the public with an sidered to be of negligible risk for members of exaggerated perception of risk from radiation. the public by the International Commission on Lord Rothschild gave in his Reith lectures a Radiation Protection. 622 Absorbed radiation in patients

TableA2.5 Effective dose equivalents

Test Activity (MBq) Absorbed dose (mSv) Risk

ChestX-ray 0.01-0.1 Less than 1 per million Renography e23I) 12 0.4 Lung ventilation (Tc) 80 0.6 Thoraeie spine 0.8 Thyroid imaging (Tc) 80 1.0 Less than 1 per 100000 Plain X-ray, abdomen 1.0 Lung perfusion (Tc) 100 1.0 Liver scan (Tc) 80 1.0 Annual natural background 1.87 Lumbar spine X-ray 2.0 Renal radionuclide study (Tc) 400 2.0-3.8 Bone scan (Tc) 400 4.0 Bariummeal 4.2 Kidney X-ray 4.5 Dynamic cardiac imaging (Tc) 800 5.6 Thallium cardiac scan 75 7.0 Barium enema 7.7 X-ray computed tomography 2-10 Less than 1 per 10 000 Coronary angiography 10-20 Less than 1 per 5000

Table A2.6 Risks of contrast material and radiopharmaceuticals

Material Risk Reference

Death from routinely used water-soluble 1 in40000 Ansen et al. (1984) intravenous X-ray contrast material Reaction to routinely used water-soluble 1 in 15 Ansen et al. (1984) intravenous contrast material lin6 Panto et al. (1986) Reaction to radiopharmaceutical 1 in2500 Keeling and Sampson injections (1975a) Reaction to penicillin 1 in 10 Keeling and Sampson (1975b)

and for 5-15 mSv: not apply to any other physical environment affecting human beings. Indeed there is ex• The study involves administration of (X-rays) (a perimental evidence of the beneficial effects of small amount of radioactivity) at a level con• low-level radiation in animals and plants on sidered to be of negligible risk for workers in longevity and fecundity, even ignoring the sup• the field of radiation by the International posed benefits of radon-containing hot-spring spa Commission on Radiation Protection. water. This beneficial effect is called radiation In the text of a submission to the Ethical Com• hormesis and the prestigious radiation protection mittee, it is proposed that the effective dose journal Health Physics has devoted a special issue equivalent in millisieverts should be stated for to this subject (Radiation hormesis, 1987). each study which involves the diagnostic use of X-rays or of a nuclear medicine procedure. A2.13 CONCLUSION Radiation is a natural phenomenon with dis• A2.12 RADIATION HORMONES advantages and benefits to man. The principle is Current absorbed radiation dose assessment is to keep diagnostic medical radiation exposures as based on the assumption that all radiation, low as reasonably practicable consistent with however low, represents a risk and that no radi• achieving a diagnostic result of good quality. This ation represents no risk. Such an argument would is best defined as the absorbed dose in milli- References 623 sieverts where 1 mSv exposure carries a risk of 17 Cornrnission on Radiological Protection, ICRP Pub• in one million. The risks of radiation used di• lication 26, Ann. ICRP 1977,1, No. 3; Ann. ICRP, 1978, agnostically are generally negligible as compared 2,No. 3. Ionising Radiation Regulations (1987) Health and Safety to the risks from the administration of standard 1985, No. 1333, HMSO, London, p. 36. medicines and from invasive or operative Keeling, D. H. and Sarnpson, C. B. (1975a) Br. J. Radial., procedures. 57, 1091-6. Kee!ing, D. H. and Sarnpson, C. B. (1975b) Drug Ther. Bull., 13, 9. Longrnead, W. A., Crown, V. P. D., Jewkes, R. J. et al. REFERENCES (1983) Radiation Protection of the Patient in Nuclear Medicine: A Manual of Good Practice, Oxford Medical Ansell, G. etal. (1984) Br. J. Radial., 57,548 (abstr.). Publications, Oxford, pp. 79-83. Brill, A. R. (1985) Low Level Radiation Effects: A Fact Book, Mole, R. H. (1987) The so called 10-day rule. Lancet, ii, Society of Nuclear Medicine, New York. 1138-40. DHSS (1988) Notes for guidance on the adrninistration Panto, P. N. and Davies, P. (1986) Br. J. Radial., 59,41-4. of radioactive substances to persans for purposes of Radiation horrnesis. Health Phys., 52, 517-680. diagnosis, treatrnent or research, Administration Sheilds, R. A. and Lawson, R. S. (1987) Effective dose of Radioactive Substances "Advisory Cornrnittee, equivalent. Nucl. Med. Commun., 8, 851-85. Departrnent of Health and Social Security, Alexander Shrirnpton, P. C. and Wall, B. F. (1986) Doses topatients FlerningHouse, London, pp. 1-32. frorn rnedical radiological exarninations in Great ICRP (1977/8) Recornrnendations of the International Britain. Rad. Prot. Bull., 7, 10-14. APPENDIX THREE Quantitativeanalysis in clinical nuclear medicine H. D. Royal and B. J. McNeil

A3.1 INTRODUCTION technology developments which have made sophisticad data analysis systems available at a enthralled by numbers Clinicians who are either reasonable cost. Secondly, improvements in somewhat in awe of them frequently or who are spatial resolution of other non-invasive modalities of tests with numerical fail tobe sufficiently critical (computed tomography and ultrasound) are re• assume that such tests have a value outputs. They directing nuclear medicine to exploit its unique higher than do tests which have only or accuracy capability for studying regional pathophysiology. outputs. While this situ• subjective or qualitative In this climate, quantitative physiological studies it is clearly not always ation is sometimes the case, will surely flourish; therefore the need for on quantitative nuclear the case. In this chapter radiologists and nuclear medicine physicians to first on objective medicine, we shall focus become aware of the fundamentals of quantitative and measurements of regional physiology tracer studies is more acute than ever. of the efficacy of di• secondly on measurements The examples of quantitative clinical studies sections we shall try to agnotic tests. In both which will be presented in subsequent sections the likely effects of emphasize basic principles, have been chosen for a variety of reasons. The math• errors in analysis and the extent to which cerebraspinal fluid shunt flow study has limited ematical approximations provide accurate application; however, its simplicity as a quantita• chapter answers to clinical problems. Since this tive model is attractive for didactic purposes. An quantita• provides only an introduction to these understanding of physical, biological and effec• is encour• tive techniques, the interested reader tive half-lives is essential in any quantitative which aged to consult other more detailed sources study; therefore these have been discussed. are listed in the references. Measurement of glomerular filtration rate pro• vides an example of a quantitative non-imaging physiological test. Regional blood flow has many TRACER STUDIES A3.2 QUANTITATIVE potential clinical applications although it has until Although nuclear medicine has its origins in util• now been primarily a research tool. Cardiac out• izing basic radiotracer principles to study non• put and transit time determination undoubtedly invasively a variety of physiology processes, the will be routinely obtained as nuclear cardiology clinical specialty has consisted primarily of subjec• becomes more refined. Finally, more sophisti• tively evaluated static images in which changes in cated methods of data analysis such as de• structure are often as important as changes in convolution are likely to be widely applied in the function. Two forces are now at work to mould future. clinical nuclear medicine into a more quantitative, Although the details of each section of this half more physiological, more dynamic specialty. of the chapter differ, the reader should recognize Firstly, for the first time in nuclear medicine's the similarity of approach in each section. When short history, sophisticated digital data acqui• faced with the task of determining a quantitative sition and analysis capabilities are becoming solution to a problem, the following approach widely available in clinical units. The impetus for should be taken. First, define the assumptions rapid dissemination of digital capabilities has upon which the solution to the problern is based. come from nuclear cardiology and from high- Secondly, assess how accurately each assumption Quantitativetracer studies 625 is met in reality. Thirdly, test the technique in a lnstantaneous lnjection broad spectrum of patients to determine what and Uniform Mixing limitations might exist.

A3.2.1 CEREBROSPINAL FLUID (CSF) SHUNTFLOW Measurement of CSF flow through ventriculo• peritoneal or ventriculovenous shunts in patients with non-communicating hydrocephalus is useful in differentiating disease progression from shunt FLOW IN EQUALS FLOW OUT failure (Rudd et al., 1973; Harbert, Haddad and McCullough, 1974). To perform this study, Figure A3.2 Assumptions underlying CSF flow cal• 500 flCi of pertechnetate in a small volume culation. This diagram shows schematically a shunt (<0.1 ml) are rapidly injected into the reservoir of reservoir with an entrance (Flow in) from the ventricles the one-way valve of the shunt appliance. and an exit (Flow out), first into the shunt tubing and ultimately into the peritoneum. The injection site for the Sequential digital images are then acquired at a radiotracer is also illustrated. Calculation of CSF shunt 1 rate of 12 frames min- for 5 min using a pinhole flow assumes that there is instantaneous injection and or parallel-hole collimator and a gamma camera uniform mixing of the tracer and also that flow into and interfaced to a minicomputer. An activity-time out of the reservoir are equal. The latter implies that the curve is generated using an operator-defined re• volume of the reservoir is constant. gion of interest over the reservoir (see Fig. A3.1). Shunt flow (ml min-1) can be measured with mixing of the tracer within the reservoir. Second• this system if the effective volume of the reservoir ly, the volume of the reservoir is constant, and, is known and if two assumptions are made (see therefore, flow into and out of the reservoir are Fig. A3.2). First, there is instantaneous, uniform equal. Under these conditions, the change in the tracer activity of the reservoir during any small 10.0~------~ time interval is equal to the flow times the tracer activity of the reservoir divided by the effective volume of the reservoir, all times the time interval. That is: t! c: (A3.1) ::1 0 u where .....Ql Q(t) = tracer activity of the reservoir (mCi) 0 L. ßQ(t) = the change in the tracer activity in the .... reservoir at time t (mCi) c: ::1 F = CSF shunt flow (ml min-1) 0 u V= effective volume of the reservoir (ml) ßt = a small time interval (min). The minus sign indicates that tracer is lost from 0 2 3 4 5 the reservoir system. Since the change in activity of tracer in the Time (min) reservoir is equal to the change in concentration Figure A3.1 Measurement of CSF shunt flow. An times the volume, equation (A3.1) can be re• activity-time curve obtained from a region of interest written in terms of concentration over a shunt reservoir is shown. The ordinate is the countrate recorded by the scintillation camera and the ßQ(t) = -ßC(t)V = -FC(t)ßt (A3.2) abscissa is time. Both scales are linear, and a mono• where exponential curve is seen. This curve becomes a straight line when plotted on a semi-logarithmic graph (see C(t) = tracer concentration of the reservoir Figure A3.3). (mCi ml-1) 626 Quantitativeanalysis in clinical nuclear medicine

AC(t) = the change in tracer concentration of the reservoir at timet (mCi ml-1) If At approaches 0, equation (A3.2) can be re• "i arranged and written in differential form as .Ec dC(t) = F -dt (A3.3) .....Vl c C(t) V ::J 0 Integration results in u .....Ql 0 t dC(t) =- fti._dt L f (A3.4) ..... 2.0 T1 = 3 min o C(t) o V c 2 ::J The solution to equation (20.4) can be found in u0 standard tables of solutions to integrals and is

1.0~--~----~-----L----~--~ 1nC(t) 1 t = _ I_ t 1 (A3.5) o V o 0 2 3 4 5 Time (minl Substituting the Iimits of the integral into equation (A3.5) and simplifying, yields Figure A3.3 Calculation of CSF flow from data pre• sented in Fig. A3.1. The ordinate is the activity recorded F lnC(t)=--t+lnC(O) (A3.6) on a logarithmic scale and the abscissa is time (min). If V the volume of the reservoir is known, the slope of the resulting straight line can be used to calculate CSF flow. Since equation (20.6) has the form of a linear CSF shunt flow (F) equals the slope times the effective equation, a graph of the logarithm of the concen• volume (V) of the reservoir. Fora Holter valve with an tration against time produces a straight line with a effective volume of 0.18 ml, the flow is 0.042 ml min-1; slope of FIV and an intercept of C(O) (see Fig. this is within the range of normal. A3.3). The slope of the straight line can be calcu• CSF shunt flow determination lated using a least squares fit; therefore, since the F = (Slope) (V) effective reservoir volume, V, can be determined experimentally, CSF shunt flow, F, can be calcu• Slope = 0.693 = 0.6~3 = 0.231 min_ 1 lated from r, 3mm F= -slope x V (A3.7) V = 0.18ml F = (0.231 min-1) (0.18 ml) Equation (A3.6) is sometimes expressed in = 0.042 ml min-1 exponential form C(t) = C(O)e(-FIV)t (A3.8) useful (Rudd et al., 1973; Harbert, Haddard and McCullough, 1974). Even in this simple example of quantitative analysis, the critical readerwill appreciate that the A3.2.2 HALF-LIVES assumptions upon which the analysis was based arenot strictly met. For example, flow through the Quantitativeanalysis of CSF shunt flow described reservoir is more likely to be pulsatile than con• in the previous section is an example of first-order stant; there may not be instantaneous uniform kinetics where the rate of change of a substance is mixing; and the injection of even a small volume directly proportional to the quantity of substance of tracer will cause a transient increase in flow. present. That is Moreover, in the more elaborate shunt ap• dQ(t) = kQ(t) pliances, eddy currents and turbulence may make (A3.9) dt the effective reservoir volume differ from the where physical reservoir volume. Despite these differ• ences between the modeland the actual Situation, Q(t) = the quantity of substance present at this technique has been found to be clinically timet (mCi) Quantitative tracer studies 627

dQ(t) -d-- = instantaneous rate of change of Q(t) t (mCi s-1) 1 k = proportionality constant (s- ) c\ c: ·c: Many physical processes demonstrate the first- ·~ 40 order kinetics described by equation (20.9). For ~ 30 example, the rate of radionuclide decay is directly :g, I I I proportional to the number of atoms present, that ~ Tl. = 3·75 h 2 eu I I QJ 20 I T!.=6·0 h r~b=10h is :: ~ . 2 1 QJ a.. I ~p V I I I dN(t) =- kN(t) (A3.10) dt I I I 10 0 2 4 6 8 10 12 where Time (h) N(t) = number of atoms present at timet Figure A3.4 Effective (T;,"), physical (T;r) and biolo• (atoms) gical half-lives (T ~). In this graph, the percentages of radionuclide remaining if only physical decay or bio• dN(t) = the decay rate (atoms s-1) logical clearance was considered are plotted as the light dt lines. The heavy black line indicates the actual per• 1 k = decay constant (s- ) centage remaining assuming that both physical decay and biological clearance occur. Typically the physical Integration and simplification, analogues to half-life is known and the effective half-life is measured. equations (A3.3-6) and (A3.8) results in Biological half-life is then calculated. As shown in the N(t) = N(O)e-kt (A3.11) sample calculations, any of the half-lives can be calculated if the other two are known. where N(O) = initial number of atoms. Since the Half-life determination physical half-life of a radionuclide is well known, equation (20.11) is more useful when k is ex• r, x r,b (10h)96h) r,," y, +T, lOh+ 6h =3.75h pressed in terms of physical half-life (Tt ). By 'P 'b definition r r, x r1," (6.0 h) (3.75 h) T~ 6.0h-3.75h =lOh r1r- r,," N(O) = _.!_ = 2 = __N--'-(0-':--) ==-- N(Tt) 0.5 N(O)e-k(Tl) r,b x r,," (10 h) (3.75 h) p r,p =6h Th,- T!eff lOh- 3.75h 1 (A3.12) where Thus, k is defined in terms of T, by taking the Q(t) = quantity at timet (mCi) natural logarithm of equation (A2.12) and re• arranging dQ(t) =total rate of loss of activity (mCis-1) dt k = -ln 2 = -0.693 (A _ )\ Tt physical half-life (s) 3 13 p = T1 T! p p Ttb = biological half-life (s) In biological systems, the disappearance of a Collected terms yields tracer is often the result of both its physical decay and its biological clearance (see Fig. A3.4). If the dQ(t) = _ ( ln 2 + ln 2 ) Q(t) (A3.lS) biological clearance follows first-order kinetics, dt Tl p Tt b the effective or observed clearance of the tracer By definition, the effective clearance rate is equal will be equal to the sum of the amount cleared to the sum of the biological and physical clearance biologically and that lost by physical decay rates ln 2 dQ(t) = -ln 2 Q(t) + -ln 2 Q(t) (A3.l4) (A3.16) dt Tt T, p 'b 628 Quantitative analysis in clinical nuclear medicine where I I rieff = effective half-life (s). INTRAVASCULAR : EXTRAVASCULAR Simplifying equation (A3.16) yields SPACE CV 1) I O SPACE CV2> r _ r!b x r! (A3.17) !eff- T +T !b !p +I Since the physical half-life is usually known and I the effective half-life is usually measured, equa• I tion (A3.17) can be written in terms of the un• I known biological half-life I I -Gfr I (A3.18) 1 I

Figure A3.5 Sapirstein's model for measurement of A3.2.3 GLOMERULAR FILTRATION RATE glomerular filtration rate. This model assumes instan• taneous intravascular injection with uniform mixing Although the clinical usefulness of measuring within the intravascular (V1) and extravascular (V2) glomerulafiltrationrate (GFR) is widely accepted, space. The rate of transfer of the tracer between spaces the existence of multiple methodologies to equals the difference between the concentrations in two measure GFR (for example, 24-h endogenaus spaces times the diffusion constant (D) (equation creatinine clearance, inulin clearance, radiotracer (A3.20)). The rate of tracer loss due to glomerular fil• clearance) indicates that each one has limitations. tration equals the intravascular concentration of tracer One commonly used radiotracer method is based times the glomerular filtration rate (GFR) (equation on Sapirstein's mode (Sapirstein, Vidt, Mandel (A3.19)). and Hanusek, 1955) to measure GFR aft~r a single intravenous injection of non-radioactive creati• The assumption that the rate of tracer loss due nine. The simplified method discussed here re• to GFR is equal to the intravascular tracer con• quires three hourly venous blood samples begin• centration times the GFR can be stated math• ning 2 h after a single intravenous injection of a ematically suitable radiopharmaceutical. Although con• troversy exists regarding the radiopharmaceutical ( dQI(t)) = GFRCI(t) (A3.19) of choice for this study, the ideal radiotracer dt GFR would have the following four characteristics: (a) where no loss of the tracer due to in-vivo metabolism; (b) no protein binding of the tracer preventing free ( dQ1(t)) = the rate of tracer loss filtration by the glomerulus; (c) small molecular dt GFR from the intravascular size; (d) no secretion or absorption of the radio• space due to GFR at tracer by the renal tubular cell. timet (mCi min-1) Sapirstein's model of GFR measurement is GFR = glomerular filtration based on five assumptions. First, the tracer mixed rate (mlmin-1) instantly and uniformly in the intravascular C1(t) = intravascular tracer space. Secondly, the tracer mixed uniformly in the concentration at timet extravascular space. Thirdly, the volumes of the (mCimin-1) intra- and extravascular spaces are constant. Fourthly, the rate of loss from the intravascular Likewise, the assumption that the rate of tracer compartment due to GFR is equal to the glomeru• loss due to diffusion is equal to the diffusion lar filtration rate times the concentration in the constant time the intravascular and extravascular intravascular space. Finally, the tracer diffusion tracer concentration differences can be stated rate between the intravascular and extravascular mathematically space varies directly with the difference in tracer dQI(t)) concentration in these areas. These assumptions ( =- D(C1(t)- Cz(t)) dt Diff are schematically illustrated in Fig. A3.5. (A3.20) Quantitativetracer studies 629

The equation is not practical to work with since where ( dQ1(t)) = rate of loss of tracer it contains the term C2 (t) which represents the dt Diff from the intravascular concentration of the tracer in the extravascular compartment due to space. Since this value cannot be measured diffusion at timet (mCi clinically, some mathematical manipulations of min-1) equation (A3.24) are needed to eliminate this D =Diffusion constant (ml term. The interested reader is referred to min-1) Sapirstein et al. (1955), Bianchi (1972) and Morgan, C (t) = extravascular tracer 2 Birks and Singer (1977) for a full derivation which concentration at timet bridges the gap between equation (A3.24) and the (mCi ml-1) following equation which states that the concen• Furthermore, the left sides of equations (A3.19) tration in the intravascular compartment is equal and (A3.20) can be expressed in terms of changes to the sum of two monoexponentials in concentration since the change in quantity of a (A3.25) substance is equal to the change in concentration times the volume of distribution where

A 1 = effective initial concentration for diffusion dQ1(t)) =V1 (dC1(t)) (A3.21). ( (mCi ml-1) dt GFR dt GFR a 1 = effective transferrate for diffusion (min - 1) where vl = the intravascular A = effective initial concentration for GFR volume (ml) 2 (mCi ml-1) a 2 = effective transferrate for GFR (min-1) = rate of change in dt GFR concentration due to The logarithm of equation (A3.25) shown GFR (mCi ml-1s-1) below, is used to calculate GFR since it is the simplest form of the equation An analogaus relationship exists for changes due to diffusion, (A3.26)

dQl(t)) As shown in Fig. A3.6 equation (A3.26) is in the ( form of the sum of two linear equations. The initial dt Diff rapid decrease in the intravascular tracer concen• Therefore, equations (A3.19) and (A3.20) can now tration is due to the rapid diffusion of the tracer be rewritten solely in terms of concentration from the intravascular space to the extravascular space. Once the extravascular tracer concen• dC1 ( (t)) = -GFR C1(t) (A3.22) tration approximately equals the intravascular dt GFR v1 concentration (point P), loss of tracer from the intravascular compartment is due solely to glom• dC1 -D and ( (t)) = - (CI(t)- Cz(t)) erular filtration. Analogaus to the calculation of dt Diff V1 F!V in the GSF shunt flow study (A3.23) GFR Since the total rate of change in concentration of az=-- (A3.27) tracer equals the sum of the rate of change due to Veff GFR and to diffusion, the following equation where emerges a2 = slope of the slow component shown in Figure (A3.5) (min-1) dC1(t)) =(dC1(t)) +(dC1(t)) ( Veff = effective volume of distribution (ml) dt Total dt GFR dt Diff -GFR D a 2 can be calculated using a least squares fit = --C1(t)- - (C1(t) through the data points afterpoint P. The effective V1 v volume of distribution can be calculated from the - Cz(t )) extrapolated y-intercept, A2, the effective initial (A3.24) concentration, since the effective volume of dis- 630 Quantitativeanalysis in clinical nuclear medicine

tribution equals the injected dose divided by the 10000 9000 effective initial concentration, that is 8000 7000 6000 (A3.28) I 5000 E where 7c: 4000 veff = effective volume of distribution (ml) E 3000 \ I GFR= -az (A3.29) 0 800 u 700 \ I Az 600 \ ~-rT:!=100min Routine clinical use of this technique is promis• 500 I I""' 2 ing; however, two obstacles must be overcome. 400 ' I Firstly, the accuracy of this method in patients 100 200 with moderate to severe renal failure who had Time (min) expanded extravascular spaces needs further validation. Secondly, an easily prepared chemi• Figure A3.6 Calculation of GFR. GFR is calculated by cally stable radiopharmaceutical which meets the determining the slope (a2) and Y intercept (A2) of the previously described criteria for an optimal GFR slow component of the blood clearance curve following agent for all pathological states is needed. a single injection of an appropriate radiopharma• ceutical. After point P (usually 2 h after injection) the effects of the fast component on the blood clearance curve are negligible; therefore the slope of the slow A3.2.4 REGIONAL BLOOD FLOW component can be determined using a semi-logarithmic The measurement of regional blood flow is based plot of the concentration-time curve. Extrapolation of on principles similar to the ones used for calcu• this curve identifies A2 as the Y intercept. The amount of lation of CSF shunt flow. The main difference activity injected (I) is determined by measuring the counts g-1of a diluted standard multiplied by the actual between the two techniques is the type of tracer number of grams of the injectate and the dilution factor. used - diffusible in the case of blood flow measurement and non-diffusible in the case of GFR determination shunt flow measurements (Fig. A3.7). Regional blood flow is measured after the intra-arterial GFR = ( ~J (Uz ) injection of a poorly soluble gas such as 133Xe, which does not recirculate because of rapid eli• 0.693 az= 0·693 = 0.00693 min-1 mination by the lungs (Kety, 1951). The injection T, lOOmin is frequently given as part of a cantrast angiogram; I= 45000000 counts min-1 to avoid the effects of cantrast on blood flow, a

A2 = 3000 counts min-1 ml-1 delay of 30-40 min between the injection of can• trast agent and Xe is common. 1 GFR = 45 000000 counts min- (0.00693 min-1) Measurement of regional blood flow using this 1 1 3000 cts min ml technique is based on four assumptions. Firstly, = 104 ml min-1 instantaneous injection of the tracer into the organ; secondly, instantaneous equilibrium be• tween blood and tissue; thirdly, no recirculation of tracer; and fourthly, an accurate measurement of organ concentration by external monitoring. Under these conditions, the regional rate of tracer loss at timet, is equal to the regional blood Quantitativetracer studies 631

where A = blood/organ partition coefficient 1 C0 (t) = organ tracer concentration (mCi mg- ) BLOOD) In addition, the organ tracer concentration equals the quantity of tracer, Q(t), in the organ divided by the organ weight, W; thereore equation (A3.30) can be rewritten

dQ(t) = -F Q(t) (A3.32) dt W'A This can be re-expressed in a form analogous to equation (A3.6) -F lnQ(t) = --t + lnQ(O) (A3.33) W'A where Q(O) = initial organ activity (mCi) () A plot of the logarithm of activity against time yields a singlestraight line with a slope of-FIW'A. Thus F Figure A3. 7 Assumptions underlying regional blood - = -'Ax slope (A3.34) flow measurement. (a) Instantaneous injection of the w diffusible radioactive tracer into the arterial blood sup• ply of the organ of interest. (b) Rapid diffusion of the Equation (A3.34) applies to regional organ flow tracer into the organ during the first passage of the bolus for organs with homogeneaus blood flow. Gener• of radioactivity. (c) Washout of the tracer from the organ ally, however, organs are more complex and con• into the veins. Note that recirculation of the tracer is sist of several types of tissues, each with their own prevented by elimination through the lungs. characteristic blood flow. In the brain (Hoedt• Rasmussen, Aveisdotter and Lasser, 1966), for example, a plot of activity against time does not yield a singlestraight line. Rather, a biexponential flow times the regional concentration of the tracer curve results (Fig. A3.8). This occurs because of in the venous blood, that is differences in blood flow between grey and white matter. Grey matter has a high blood flow (A3.30) (78.0-80.5 ml min-1 per 100 g tissue) whichcauses a rapid washout of the tracer. White matter has a where lower blood flow (18.7-21.1 ml min-1 per 100 g) Q(t) = regional amount of tracer (mCi) and hence a slower washout. These two com• ponents can be separated mathematically either dQ(t) = the regional rate of loss of the tracer by simple curve stripping or by a more compli• cated procedure using a non-linear least squares dt (mCi s-1) fit (Deli, Sciacca, Lieberman, Case and Cannon, F =regional blood flow (ml s-1) 1973). Cv(t) = concentration of tracer within the An alternative mathematical approach to the venous blood (mCi ml-1) measurement of regional systemic blood flow us• Since extemal monitaring measures organ con• ing washout has been proposed by Zierler (1965). centration (assumption 4), not venous concen• It is based on the principle that over all time, the tration, equation (A3.30) must be expressed in change in the amount of tracer, dQ(t), must equal terms of organ concentrations. Venous blood• the efferent flow times the efferent concentration, organ concentrations are related in the following that is manner födQ(t) =-föFCv(t)dt (A3.35) 'A= (A3.31) Equation (A3.35) is identical to equation (A3.30), except that integration has been per- 632 Quantitative analysis in clinical nuclear medicine

10 ponents representing blood flow to the white and grey 9 8 matter are apparent. The relative blood flow can be 7 determined from the slopes of the two components of 6 the washaut curve if the blood/tissue partition co• 5 efficients are known. These blood/tissue partition co• 4 \ efficients can be determined experimentally and tables \ containing their values are available. Blood flow is cus• 3 -\.. ... I '• tomarily determined per 100 g of tissue . c I '• Regional blood flow determining (slope method) E 2 \ '" FIW = ( -A.) (Slope) ...... Ul c Grey matter ::J 0 u A. = 0.77 ___m_l __ I g grey matter QJ 9 ...... 8 e 7 Slope = -0.693 = 0.693 1.03 min-1 6 7i = 5·0 min r, 0.67min ...... "2 c 5 ::J ml 0 ~r1 = 0·67 min FIW = 0.77 -----"--(1.03 min-1) u 4 I - g grey matter \ 2 3 \ (100 g grey matter) = 79.3 ml min-1 2 White matter ml A. = 1.44 \ g white matter 5 I 0 15 Time (min) Slope = - 0·693 = 0·693 0.139min-1 T1 5.0 min ml Figure A3.8 Typical brain washaut curve after an in• FIW = 1.44 -~,.,----,.,....-- (0 .139 min - 1) ternal carotid injection of 133Xe. The count rate-time g white matter curve representing washout of activity from the brain = (100 g grey matter) following an intra-arterial injection of radioactive xenon is plotted on a semi-logarithmic graph. Two com- = 20.0mlmin-1

formed. Substituting (1/(A.Q)/Q(t) for Cv(t) (see A = area (JQ(t )dt) und er the washout curve from equation (A3.31)) and rearranging terms, yields t equals 0 to oo . The tissue blood coefficient (A.) can be deter• "' dQ = ~J"' Q(t )dt (A3.36) mined experimentally. Jo A.W o The height of the washout curve is proportional Solving the integration of the left-hand side of to Q(O) and the area under the washout curve is equation (A3.36) yields proportional to f0Q(t )dt. Since the same detector geometry is used to measure both, relative flow Q(O) = _F_J"' Q(t )dt (A3.37) (F/W) is equal to the blood tissue coefficient (A) A.W o times the height of the washout curve divided by Rearrangement yields equation (20.38) which its area. In Fig. A3. 9 shows component of the expresses relative flow (F/W) in terms of the washout curve from Fig. A3.8 (T! = 5.0 min) has measured variables, Q(O) and f;';'Q(t )dt been replotted on a linear graph. The height over area method yields the same relative flow as was I_ Q(O) A.H (A3.38) obtained using the slope method. W f;';'Q(t )dt A where H = height (Q(O)) of the washout curve Quantitative tracer studies 633

32 00 TableA3.1

c Measured '.E Cardiac Output Ejection Fraction 1!! c Mean Pulmonary Transit Time :J 0 Total Blood Volume 0 Derived 1!. End Diastolic Volume ...c End Systolic Volume c Pulmonary Blood Volume :J 0 u 0 10 20 30 Time (min) these measurements is needed. In-vitro labelled red cells prepared with the Brookhaven kit cur• Figure A3.9 Regional blood flow determination rently come closest to meeting this need. Second• (height/area method). The slow component from the biexponential curve obtained in Fig. 14.8 is plotted here ly, externally monitared activity-time curves must on linear paper. Note that the samerelative flow which accurately reflect intravascular concentration• was obtained using the slope method in Fig. A3.8 is time curves. Problems related to detector geo• obtained using the height over area method. Regional metry and deadtime at high count rates with an blood flow determination (height/area method) Anger camera need tobe resolved. H Cardiac output determinations are based on the F/W = (A.) A principle of conservation of mass (Donato et al., 1962a, b; Lewis, Guintini, Donato, Harvey and ml A. = 1.44 Cournand, 1962; Kaikka, Timisjarvi and g white matter Tuominen, 1979). If a non-diffusible, non• H = 32000 counts min-1 metabolizable tracer is used, the amount of tracer A = 229 200 counts entering the heart must equal the amount of tracer leaving the heart. The amount of tracer entering FIW = ( 1.44 . ml ) the heart is equal to the total amount of the tracer g whJte matter injected. The amount of tracer leaving the heart region of interest in any small time interval is 32000 counts min-1 ) (100 h"t t ) equal to the concentration of the tracer ( 229 000 counts g w 1 e ma ter at that time times the cardiac output times the time interval. = 20.0 ml min-1 The total amount leaving the heart is equal to the sumofall the amounts that left during all of the small time intervals. Mathematically A3.2.5 CARDIAC OUTPUT Q = "2:-FkC(t )/H (A3.39) During the past several years, cardiovascular where nuclear medicine has grown dramatically. See also chapter 1. An important index of cardiac Q = the total amount of tracer injected (mCi) function, cardiac output, can be obtained non• F = cardiac output (ml min-1) invasively in conjunction with a first-pass radio• k = proportionality constant to convert counts nuclide angiocardiogram performed alone or min-1 to mCi ml-1 performed prior to grated equilibrium cardio• vascular studies. In fact, if cardiac output, ejection ~~ cou~ts) ( ml mm fraction, mean transittime (see the next section) and total blood volume are known, all of the C(t) = externally monitored countrate of the cardiac indices listed in Table A3.1 can be deter• tracer leaving heart region of interest at mined non-invasively. timet (counts min-1) Two problems need to be solved, however, ßt = small time interval (min) before the simultaneaus radionuclide measure• As 11t approaches 0, ment of cardiac output and ejection fraction equation (A3.39) can be integrated is widespread. Firstly, a 99mTc-labelled radio• pharmaceutical which can be used for both of Q = Fkf0C(t )dt (A3.40) 634 Quantitativeanalysis in clinical nuclear medicine

Estimation of cardiac output requires knowl• edge of the proportionality constant k. This is difficult to measure since it changes with each patient and with each detector. However, if equilibrium measurements are made using the same detector geometry used to measure concen• tration changes, then the following relationship exists ....Q) ....0 .... (A3.41) c: ::J where 0 u Ceq = countrate at equilibrium in the heart 14 2 5 1 (s) (min) region of interest (counts min - ) Time V = total blood volume (ml). Figure A3.10 Cardiac output determination. The Substituting equation (A3.41) into (A3.40), sim• count rate-time curve from a region of interest of the plifying and rearranging leads to the elimination heart is plotted. The crosshatched area under the curve of k in the final expression. Thus is a graphic representation of the area under the curve when the upslope and downslope have been extra• CeqV F= (A3.42) plated to zero. The total blood volume (V) is calculated JO'C(t )dt from simple dilution principles. Since the injected dose (Q) contains several thousand times the amount of The total blood volume can be determined by activity as the equilibrium sample (E), an aliquot of the simple dilution principles if the red cells have injected dose is usually carefully diluted one thousand• been labelled in vitro with high efficiency. fold to assurealinear response of the well counter. Once The use of equation (A3.42) in measured cardiac total blood volume is known, cardiac output can be output is described in Fig. A3.10. In this example determined by measuring the count rate at equilibrium 15 mCi of Tc-labelled red cells were injected (Q). A (C.9) and the area under the countrate-time curve. In blood sample obtained at equilibrium contained order to eliminate the effects of background and recir• culation the countrate-time curve must be extrapolated !!Ci ml-1; therefore, the total blood volume (V) 3 to zero. was 5000 cm3 . To calculate cardiac output the equilibrium concentration, Ceq' and the area Cardiac output determination under the activity-time curve are needed. The F = (C.9 ) (V) curve has two peaks representing the passage of fi)C(t)dt the bolus through the right and left side of the Q 15 heart (see Fig. A3.10). When corrections for back• V= E mCi = 5000 ml ground and recirculation were made by extrapo• 3f!Ciml 1 1 1 lating to zero, the area was found to be 130 000 C.9 = (2000 counts s- ) (60s min- ) counts-s. The count rate at equilibrium, Ceq' was = 120000 counts min-1 determined several minutes after the injection of the tracer using the same region of interest and f0C(t)dt = 130000 counts without moving the patient. In performing this F = (120000countsmin-1)(5000ml) technique, it is important to note that the gamma (130000 counts) camera must have a linear response over a several• fold range in count rates (that is, 2000-18000 = 4615 ml min-1 counts s-1) if accurate results aretobe obtained. Excessive deadtime will result in underestimation of the denominator of equation (A3.42) and there• sit times because they can be used to estimate fore will overestimate cardiac output. pulmonary blood volume. The calculation of tran• sit times can be understood if the flow of a non• diffusible radioactive marker travelling with a A3.2.6 TRANSIT TIMES velocity, v, through a pipe of length, L, and an The current popularity of first-pass radionuclide area, A, is considered (Fig. A3.11) (McNeil, angiocardiography has stimulated interest in tran- Holman and Adelstein, 1976). If the quantity of Quantitativetracer studies 635

(a) L v = velocity of flow (cm s-1) A = cross-sectional area of the pipe (cm 2) ()~, (A) and because v = L!t (A3.44) )~ where L = length of the pipe (cm) t = transittime (s)

F= LA = ~ (A3.45) t t where V= volume (ml) "'Q~ (t) and, on rearranging, -v (b) V y, • V t= (A3.46) F -v ~ The transit time, t, then equals the volume of -v the pipe divided by its flow. This generality -v applies to all intravascular (non-diffusible) indicators. f? For real systems the situation is more complex ---a.w because several paths through the conduit are (cl (d) possible (Fig. A3.1lb). In such cases, a distribu• tion of counts against time is expected at the exit Single pathway Many pathways (Fig. A3.11d); those tracer molecules appearing at earlier times will have traversed a shorter total path length than those appearing at later times. Thus, there is no single transit time but rather many transit times with a mean transit time, t. located at the centre of gravity of the activity-time plot. Mean transit time is equal to the integral of the activity at time t times the time divided by the 1\ integral of the acitivity-time curve + t •t - f;5'Q(t )tdt Figure A3.11 Transit time. Transit of tracer through a t= ---- (A3.47) single pathway (a) yields a single transit time, t (c). f;5'Q(t)dt Transit of tracer through many pathways (b) yields a where mean transit time, t (d). (Reprinted with permission from Diagnostic Nuclear Medicine edited by Alexander t = mean transit time Gottschalk and E. J. Potchen, MD, Williams and Wilkins Q(t) = activity at time t (mCi) Company, Baltimore.) t = time from the initial input of activity (s) Equation (A3.47) is called the first moment of the activity-time curve. nuclide appearing at the exit is monitored as a An example function of time, no activity is registered at the exit of the calculation of mean pulmon• ary transit time is shown while the marker is in the pipe; once the tracer in Fig. A3.12. A time activity plot from a region leaves the pipe, counts are registered. The time to of interest over the lungs is obtained. The upslope transverse the system from entrance to exit is the and downslope of transittime (Fig. A3.1lc). the pulmonary curve must be extrapolated to zero activity to eliminate the Because flow, F, can be related to velocity by effects of background and recirculation and, thus, obtain a finite value from F = vA (A3.43) the integral of the curve, Typically, the extra• where polation of the upstroke is linear, whereas the extrapolation of the downslope is mono• F = flow of the tracer (mls-1) exponential. Once this extrapolation has been 636 Quantitative analysis in clinical nuclear medicine

vp = Ftp (A3.48) where vp = pulmonaryblood volume (ml) .! = cardiac output (mls-1) tP = mean pulmonary transit time (min) Since cardiac output and mean pulmonary tran• be calculated using first-pass radio• ....ll) sit time can c nuclide angiocardiography, an estimate of :l 0 pulmonary blood volume, which may be useful in u evaluation of left ventricular failure, can also be obtained...... <11 ....0 An alternative approach to the measurement of ..... mean transit time has been proposed, analogous c :l tothat described in the measurement of regional 0 u blood flow (Zierler, 1965). It states that - A t = -- (A3.49) A.aH where

0 5 10 A = area under the washout curve Time (s) H = initial height of washout curve Figure A3.12 Calculation of mean pulmonary transit A. = the blood/tissue partition coefficient time. A countrate-time curve is obtained over the lungs a = tissue density, which for most tissues is after a bolus injection of radiotracer. The activity-ti,me approximately 1. Therefore, equation curve is extrapolated to zero to eliminate the effects of (A3.49) can be simplified to recirculation (dashed curve). The background and - A crosshatched area graphically represents the integral of t = -- (A3.50) the extrapolated countrate-time curve. The integrals in A.H equation (A3.47) are calculated from this extrapolated curve and are used to determine mean pulmonary The concept of transit time has been confused transit time. because two other indices which can easily be calculated have been popularized. In addition to Mean pulmonary transittime determination mean transit time, peak-to-peak transit time and MPTT = JO'Q(t)tdt mean pooltransittime are routinely calculated by JO'Q(t)dt one major manufacturer's software for first-pass radionuclide angiocardiograms. Although these 1 JO'Q(t)tdt = 180000 counts s- two indices are proportional to mean pulmonary J0Q(t)dt = 30000counts transit time, the proportionality constant is un• known; therefore, the desired measurement of t = 180000 counts s-1 = 6 5 volume cannot be made. 30 000 counts pulmonary blood Measurement of peak-to-peak transit time is illustrated in Fig. A3.13. For this purpose, performed, mean transit time can be calculated activity-time curves from right and left ventricular using equation A3.47. regions of interest are superimposed. The Furthermore, as implied in equation (A3.46), peak-to-peak transittime is equal to the difference pulmonary blood volume can be calculated if pul• in the times that peak activity is in the 'right and monary flood flow and mean transit time are left ventricles. known. Mathematically, pulmonary blood Calculation of the mean pool transit time is volume equals pulmonary blood flow times mean slightly more complex than calculation of peak-to• pulmonary transit time. In patients without peak transit time. This index measures the differ• shunts, pulmonary blood flow equnls cardiac out• ence between the time when the maximum put; therefore activity enters and the time when it leaves the Quantitativetracer studies 637

t 2 ( a) t, I ·-•- Right ventricular activity -time curve ltll

__ Left ventricular Ul Cl) ..... activity -time curve c: 2 :::J c 0 0 u u" Ql +- ~ c a L...... L...... c c: :::J 0" 0 u (.)

Time (s) 15 0 15 Time (s) ( a) Figure A3.13 Peak-to-peak transit time (T). The dashed curve represents activity-time curve from a N 'Ul region of interest over the right heart. The solid curve 2 represents an activity-time curve from a region of in• c: terest over the left heart. The peak to peaktransittime is :::J 0 calculated by subtracting the time that peak activity u occurs in the right ventricle (t1) from the timethat peak activity occurs in the left ventricle (t2). These times are determined from right (-·-·) and left (-) ventricular activity-time curves following a bolus injection of a radiotracer. Peak to peak transit time determination Figure A3.14 Mean pulmonary pool transit time. T = t2 - t1 = 8.5 s - 3.5 s = 5.0 s Curve A represents an activity-time curve from a region of interest over the lungs. Curve b represents the first derivative of curve a. Mean pulmonary transit time region. The upper curve in Fig. A3.14 is the equals the difference between the time when the maxi• pulmonary activity-time curve; the lower curve is mum activity enters (t1) and leaves the Jung. Since the first derivative (curve the first derivative of the upper curve. b) corresponds to the instan• The pool taneous slope of the pulmonary transit time is activity-time curve equal to the difference between the (curve a), the times of maximum upslope and down• time of maximum upslope and maximum down• slope can be easily calculated from the peaks and valleys slope. Since the firstderivative (the lower curve) of the first derivative. corresponds to the instantaneous slope of the Mean upper curve, the times of maximum upslope and pulmonary pool transit time determination maximum downslope of the upper curve can easi• T = t2- tr ly be calculated from the peaks and valleys of the T = 10 s - 5 s = 5 s lower curve. depend not only on the organ function (the organ response) but also A3.2.7 CONVOLUTION AND on the manner in which the DECONVOLUTION tracer arrives in the organ (the input function). Deconvolution analysis eliminates the effects of Although convolution and deconvolution analy• the input function and, therefore, allows more sis has been widely applied in many quantitative accurate investigation of organ response. fields, these techniques have only recently been To understand this analysis, let us first look at utilized in the analysis of cardiac (Alderson et al., the interaction of a hypothetical input function 1979) and renal radiotracer studies (Kenny, and organ response function (see Fig. A3.15). Ackery, Fleming, Goddard and Grant, 1975; Assurne that the input to the organ is instan• Diffey, Hall and Corfield, 1976). In all dynamic taneous and that the area under the input function studies, observed organ activity-time curves is equal to 1.0. This theoretical input function is 638 Quantitative analysis in clinical nuclear rnedicine

100 Count rate Count ra~e ( counts s-1) (counts 5 1)

0 5 10 15 Organ 0 5 10 15 Time (s) response Time(s)

100 Coun~ rate 1 (counts s- ) 50

0 5 10 15 Time(s) Figure A3.15 The relationship of the input function, organ response and output function. If the input function (the bolus injection) illustrated in the upper left and the output fraction (the activity-time curve for the organ of interest), illustrated in the upper right, are externally monitored, the organ response (below) can be calculated. In the example shown here, the output function is identical to the organ response since the input function is instantaneous (spike or delta function). called a delta or spike function. Let us further A3.16c. This process of summing the organ re• assume that the organ of interest instantaneously sponse and input product is called convolution. A extracts 50 per cent of the injected tracer, that the dashed line connecting the points in Fig. A3.16c minimum time it takes for the tracer to pass reveals that the shape of the output function can through the organ is lOs, and that the elimination be affected much more by the input function than of the tracer from the organ is linear. With an by the organ response. instantaneous input, the output function is equal Mathematically, a continuous input function to the organ response. Generally, instantaneous can be treated as an infinite number of instan• input functions do not exist; therefore, in practice, taneous inputs; therefore any input function can the output function never equals the organ be convoluted with any organ response to yield an response. output function. Likewise any output function A continuous input function can be approxi• can be deconvoluted so that the organ response is mated by multiple instantaneous input functions. identified if the input function is known. The In Fig. A3.16a, five instantaneous input functions, actual mathematics of the convolution and decon• lOs apart, have been used to approximate a con• volution processes are beyond the scope of this tinuous input function (dashed curve). The organ text. The formal mathematical statement of the response from each of these five instantaneous convolution process is as follows inputs is shown in Fig. A3.16b. Under these con• C(t) = I(T)H(t- T)dT (A3.15) ditions the output function equals the sum of the fo organ responses to multiple instantaneous in• where C(t) = output function puts. The sum of the organ responses in Fig. I(T) = input function A3.16b at six different times is indicated in Fig. H(T) = system (organ) response Quantitative tracer studies 639

100 (al (b) (c) ~ ~ Abnormal Abnormal ~ ' Normal 50 ,; ' ' Input Function ,; .... ,; .... ,...... Cl> .... +' 0 ... «< I -10 0 10 20 30 40 50 0::: II) +' (a) c: II) :::J ...... 0 c () ::::l 0 [SjEJU u Time (Min) INPUT FUNCTION Q) ...... Cl> c +' L.. ,::1 «< .._ 0::: c I +' ::::l -10 0 10c=f\ 20 30es 40P ,'50 c: 0 :::J 0 u (b) () Time (Min) OUTPUT 00 FUNCTION ...... Cl> ,. ~ ..... +' 50 ,. ' «< ",.,. ' 0::: ",...... +' f1' " ...... c: :::J 0 0 -10 0 10 20 30 40 50 () (c) Time (s) DDDTime (Min) Figure A3.16 Effects of a continuous input function on ORGAN RESPONSE the output function. (a) The countrate-time curve of a continuous input function is illustrated. A continuous Figure A3.17 Usefulness of deconvolution analysis of input function can be treated mathematically as an renograms. The count rate-time curves for the input infinite series of instantaneous input functions. For function, the output function and the organ response simplicity only five of the instantaneous input functions are illustrated for a normal renogram, an abnormal used to approximate the continuous input function are renogram due to an abnormal input function, and an shown. (b) The instantaneous organ response to the five abnormal renogram on all graphs. Column (a), normal instantaneous input is illustrated. (c) The externally input function, normal output function (renogram), monitored output function equals the sum of the organ normal organ response. Column (b), abnormal input responses illustrated in (b). The shape of output func• function due to the subcutaneous injection of the radio• tion can be more profoundly affected by the input pharmaceutical. Abnormaloutput function (renogram) function than by the organ response. due to the abnormal input function. Normal organ response after deconvolution. Column (c), abnormal input function revealing delayed blood clearance due to poor renal function. Abnormal output function (reno• These calculations are performed relatively easily gram) due to abnormal organ response and the resulting on computers by using fast Fourier transforms abnormal input function. Organ response is clearly which change the complex process of con• abnormal after deconvolution indicating the abnormal volution/deconvolution to multiplication and output function was not due soley to an abnormal input division, respectively. function. An obvious but sometimes overlooked Iimit• ation of deconvolution analysis is that this tech• nique is valid only if the input and output meaningless. Since bolus injections are generally functions are accurately known. If the externally used, determination of the input function can be monitored activity-time curves from regions of particularly difficult. Monitaring activity from a interest are inaccurate due to poor statistics or due region of interest over the heart would give the to contamination by activity from surrounding best counting statistics but would not accurately structures, then the deconvolution will be reflect the input function of an organ which is 640 Quantitativeanalysis in clinical nuclear medicine

some distance from the heart. By the time the nique for the analysis of kinetic data and its appli• bolus reached the organ it would have spread out. cation in the study of renal 133 Xenon washout in The time delay from the heart to the organ would dogs and man. Circ. Res., 32, 71-84. Diffey, B. L., Hall, F. M. and Corfield, J. R. (1976), The also be unknown. Because of these problems, the 99mTc-DTPA dynamic renal scan with deconvolution input function is measured as close to the organ of analysis. J. nucl. Med., 17, 352-5. interest as possible. For renal studies, a region of Donato, L., Guintini, C., Lewis, M. L., Durand, J., interest over the abdominal aorta is used to deter• Rochester, D. F., Harvey, R. M. and Coumand, A. (1962a), Quantitative radiocardiography I mine the input function. This approach intro• theoretical considerations. Circulation, 26, 174-82. duces uncertainties because the counting statistics Donato, L., Rochester, D. F., Lewis, M. D., Durand, J., are poor, background activity is high and small Parker, J. 0. and Harvey, R. M. (1962b), Quantitative changes in positionwill cause great changes in the Radiocardiography - II technical analysis of curves. detected activity. Since the deconvolution analy• Circulation, 26, 183-8. Fleming, J. S. and Kenny, R. W. (1977), A comparison of sis is very sensitive to aberrations in the input techniques for filtering noise in the renogram. Phys. function, some processing of the raw data to re• Med. Biol., 22, 359-64. move some of these aberrations is often needed Harbert, J., Haddad, D. and McCullough, D. (1974), before the deconvolution can be performed Quantitation of cerebraspinal fluid shunt flow. Radiology, 112, 379-87. (Fleming and Kenny, 1977). Hoedt-Rasmussen, K. Aveisdotter, E. and Lasser, N. Examples of the clinical usefulness of decon• (1966), Regional cerebral blood flow in man deter• volution analysis of renograms is shown in Fig. mined by intra-arterial injection of inert gas. Circ. A3.17. A normal input function, renogram and Res., 18, 237-47. Kaikka, J., Timisjarvi, J. and Tuominen, M. (1979), deconvoluted renogram are shown in (a), an Quantitative radiocardiographic evaluation of cardiac abnormal input function (due to a subcutaneous dynamics in man at rest and during exercise. Scand. J. injection), the resulting abnormal renogram and clin. Lab. Invest., 39, 423-34. the deconvoluted renogram are shown in (b ), and Kenny, R. W., Ackery, D. M., Fleming, J. S., Goddard, an abnormal input function (due to poor renal B. A. and Grant, R. W. (1975), Deconvolution analysis of the scintillation camera renogram. Br. J. Radial., 48, function), and abnormal renogram and the decon• 481-6. voluted renogram are shown in (c). Since the Kety, S. S. (1951), The theory and applications of the height of the deconvoluted renogram is pro• exchange of inert gas at the lungs and tissues. portional to renal function, and since the transit Pharmac. Rev., 3, 1-47. Lewis, M. L., Guintini, G., Donato, L., Harvey, R. M. time increases with decreased renal function, the and Coumand, A. (1962), Quantitative radiocardio• deconvoluted renogram can be used to differenti• graphy - III results and validation of theory and ate between normal and abnormal renal function method. Circulation, 26, 189-99. independent of the input function. Note that not McNeil, B. J., Holman, B. L. and Adelstein, S. J. (1976). only does an abnormal input function cause an In Theoretical Basis for Blood Flow Measurement in Di• agnostic Nuclear Medicine (eds A. Gottschalk and J. abnormal renogram (b) but also that abnormal Potchen), Williams and Wilkins, Baltimore, eh. 13. renal function causes an abnormal input function Morgan, W. D., Birks, J. L. and Singer, A. (1977), An (c) because of slower blood clearance. efficient technique for the simultaneaus estimation of GFR and ERPF, involving a single injection and two blood samples. lnt. J. nucl. Med. Biol., 4, 79-83. REFERENCES Rudd, T. G., Shurtleff, D. B., Loeser, J. D. and Nelp, Alderson, P. 0., Douglass, K. H., Mendenhall, K. G., W. B. (1973), Radionuclide assessment of cerebra• Guadini, V. A., Watson, D. C., Links, J. M. and spinal fluid shunt flow in children. J. nucl. Med., 14, Wagner, H. N. (1979), Deconvolution analysis in 683-6. radionuclide quantitation of left and right cardiac Sapirstein, L. A., Vidt, D. G., Mandel, M. J. and shunts. J. nucl. Med., 20, 502. Hanusek, G. (1955), Volumes of distribution and Bianchi, C. (1972), Radionuclides in Renal Evaluation, clearances of intravenously injected creatinine in the Vol. 2, Basel and University Park Press, Baltimore, dog. Am. J. Physiol., 181, 330-6. pp. 21-53. Zierler, K. L. (1965), Equations for measuring blood Dell, R. B., Sciacca, R., Lieberman, K., Case, D. and flow by extemal monitaring of radioisotopes. Circ. Cannon, P. J. (1973), A weighted Ieast-squares tech- Res., 16, 309-21. Index

Page numbers in italics refer to figures and tables

Abdominal abscess 304-5 cause 117 scan 598 Abdominal infection and radionuclide imaging 118-19 scintigraphy 271, 288-9 inflammation 304-5 Acyl-CoA:cholesterol syndromes of hormone excess Abdominal pain 334-5 acyltransferase (ACA T) 272 271 Abdominaltrauma 315, 317 Adjuvant chemotherapy 441, tumours 435-6 approach to treatment 315 442-3 venography 271 computerized tomography Administration of Radioactive Adrenal medulla 280-6 (CT) 315 Substances Advisory neuroblastoma 287-8 liver evaluation 318 Committee (ARSAC) 566 neuroendocrine tumours nuclear medicine techniques Adrenal cortex 272-80 287-8 315 computed tomography (CT) phaeochromocytoma 281-4 radionuclide angiography 317 279 physiology 280-1 renal abnormalities 317 Cushing's syndrome 274-6 Adrenal medullary tumour 436 SPECT imaging 317 drug history in scintiscan 1311-meta-iodobenzylgyanidine spieen evaluation 318 interpretation 274 (MIBG) therapy 613 ultrasonography 315 hyperplasia 277-8 Adrenaline 281 Absorbed radiation in patients: a incidental adrenal mass 279-80 secretion from adrenal memorandum for the ethical physiology 272 medullary tumours 436 committee 606-8 primary hyperaldosteronism Adrenergic receptors 30-1 Acetylcholine receptor imaging 276-8 Adrenocorticotrophic hormone 527 radiocholesterol uptake 273 (ACTH) 272 Achalasia 292 radiopharmacology 272-74 adrenal cortical hyperplasia Acoustic neuroma 430, 518 regulation of cholesterol pool 274 Acquired immunodeficiency and hormone biosynthesis radiocholesterol uptake 273 syndrome (AIDS) 272 Adult respiratory distress alveolar clearance assessment scintigraphic findings 280 syndrome (ARDS) 48 65 tumours 274, 276, 436 Aflatoxin 426 dementia 186, 187 virilism 278-9 Agranulocytosis 208 gallium imaging of lungs 65-6 Adrenal gland 271 Air embolism 60 neurological manifestations anatomy 271 Alactasia 302 158 arteriography 271 Albumin 239 pulmonary infection 65 computed tomography (CT) Aldosterone 92, 271 Active non-ATPase-independent 271 antagonism 273 sodium pump, 111 magnetic resonance imaging Aldosteronoma 276, 277 Acute tubular necrosis (ATN), 271 Alveolar capillary membrane 48 116, 117, 123-4 metastasis 429 Alveolar pressure 48 642 Index

Alzheimer's disease 186, 187, Anilino-naphthaline sulphonic a 1-antitrypsin deficiency 64, 64, 510-11 acirl (ANS) 239 327, 336 CBF impairment 166, 179 Ankylosing spondylitis bone Aortic aneurysm 76, 78 SPECT imaging 181 scan 149 Aortic flow, abrlominal78, 79 99mTc-labelled HMPAO CBF Antegrarle perfusion pressure Aortic regurgitation SPECT 188 measurement (APPM) asymptomatic 14 treatment 188 110-11 bloorl pool imaging 13-14 Amine Precursor Uptake and Anti-CEA antiborlies 62 Aortic stenosis 13 Carboxylation 288 Anti-hepatitis antibody 522 Apical aneurysm 16 Amino acid metabolism in Anti-melanoma antiborly 485 Aplastic anaemia, ferrokinetics tumour growth assessment Anti-myosin 522 359, 360 451 Anti-T3 antisera 244 Apurlomas 288 Aminopterin 479 Anti-T4 antisera 244 Arachnoirl cyst 192 Amiodarone 207 Anti-TSH Arterial obstruction 76 iodine-induced antiborly 236, 237 Arteriographie anatomy 85 hyperthyroidism 212 receptor antiborlies 252 Arteriography of bone tumours Amoebic abscess 335 Anti-tumour antiborlies 507 442 Anaemia 297 Antiborly Arteriosclerosis 367 blood volume measurement anti-tumour 507 Arteriosclerotic plaques 370 347 bispecific in Arteriovenous shunt Analgesie nephropathy 103 rarlioimmunotherapy 499 measurements 88 Analog-to-digital converters 553 enzyme labelled 481 Arthritis Analogue imaging 555, 561-2 indium labelling 488-9, 490 bone scan 149-50 Anaplastic thyroid in radioimmunoscintigraphy temporamandibular joint 467 cancer 435 523-4 Arthropathy, peripheral149 carcinoma 217, 227 rarlioiorline labeHing 488 Asbestos inrlustry 437 Androgens 271 rarliolabellerl 481 Asbestosis 48 Androstenedione 271, 278 residence time on tumour 497 99mTc-labellerl DTP A aerosol Aneurysm speed of use of labelled 498 clearance 65 blood pool imaging 12 technetium labelling 489, 491 Ascites 336 false 12 uptake 485 Ascorbic acid 355 Anger camera 9, 543-4, 547 Antidiuretic hormone 93 Aspergillus flaveus 426 crystals 545 Antigen-antibody interactions Aspirin 297 energy spectrum 545 236 Assessing Medical Technologies 580 environment 558 Antigens in Asthma 295 flood field correction 545 radioimmunoscintigraphy Astrocytoma 173, 429, 430 real-time correction system 546 522 Ataxia telangiectasia 615 resolution 544, 545 Antimicrosomal antiborlies 251-2 Atheroma rletection 30 spatial distortion 545 Antimyosin 26-7 Atrial fibrillation 210 SPECT capability 556 Antithyroglobulin antiborlies Atrial myxoma 15 Angina, unstable 11 251-2 Atrium 2 Angiocarrliogram, rarlionuclirle Antithyroirl rlrugs 201 enlargement in tricuspirl valve 418,420 elrlerly patients 210 disease 14 shunt quantification 420 foetal effects 210 atrophic carrliomyopathy 422 Angiodysplasia 296 Graves' rlisease 208 Attributahle risk 617 Angiography 75, 76 intrathoracic goitre 221 I9BAu hepatic 322 perchlorate discharge test lymph norle scanning 503 Angiotensin 92 230 see also Gold converting enzyme (ACE) 92 in pregnancy 209 Autoimmune thyroiditis 202 Angiotensin II 108, 273 sirle effects 208 A vascular necrosis Angiotensinogen 273 thyroirl activity rluring anrl bone infarction 150 Aniline rlye inrlustry 427 treatment 211 of the femoral hearl 391, 394 Index 643

SPECT imaging 152 first-pass 9-10 sex 384 Axillary lymph node scanning head and neck assessment 460, studies 387-8 506-7 461 tonicity disturbance 386 Axillary lymphoscintigraphy, 441 prognosis 13 whole-body neutron activation Blood volume 346-47 388 ß-adrenergic blocking drugs 200, clinical indications for Bombesin 298 208 measuring 347 Bone B-lymphocyte 524 expression of results 349-50 diphosphonate uptake 152 Background subtraction 492 plasma volume measurement graft viability 515, 516 Bacterial overgrowth of small 348-9 imaging 394, 396, 519-21 bowel302 red cell volume 347-8 infection 144-9 Baker' s cyst 82 reference values 349 neoplasms 398-400 Barium meal 300, 301 Blood-brain barrier (BBB) 159 osteosarcoma 427 Barrett's oesophagus 292, 299 breakdown 173 scintigraphy 161, 442 detection 306 Blood-brain barrier (BBB) scan Bone marrow Bayes theorem 574 158, 169-88 imaging 378-9 Bed rest 77 CBF autoregulation 185 ionizing radiation 426 Benefit-risk ratio 613 cerebral abscess 178 radiosensitivity 497 Benotti R., 49 cerebrovascular disease 176 scan 602 Benzidine 427 chronic subdural haematoma Bone metastases 441, 442, 444-5, Benzodiazepine receptor studies 176-7 494 192 dementia 186-8 67Ga imaging 447 3,4-benzpyrene 427 dynamic study 170 lung cancer 143-44 Bhopal620 epilepsy 186 1S6Re-labelled EHDP therapy Bile tests 308 false-positive brain scan 178 531 Biliary tract 321 1231-4-iodoantipyrine, 162 scanning 135, 463 atresia 401, 405 1231-IMP CBF scan 180 1S3Sm-labelled EDTMP therapy disease in children 401 migraine 185-6 531 drainage assessment 341 neoplasia 186 spread 428-9 investigations 324 patient preparation 169 Bone pain 135, 144, 530-1 obstruction 331 planar imaging 180-1 palliation 453 radiography 324 radiopharmaceuticals 161-2 Bone scan 131, 595 Rose Bengal investigation 341 static brain scan 170 ankylosing spondylitis 149 Binswanger's disease 186 99mTc-labelled HMPAO CBF arthritis 149-50 Bisacodyl288 scan 180, 183 avascular necrosis and hone Blocking antihoclies 222 technique 170 infarction 150 Blood tomographic imaging (SPECT) children 392, 399 pressure 1 181 equipment 131-2 velocity measurement 1 133Xe CBF SPECT scan 179-80 infection 147-9 Blood flow B 3Xe CBF study, 178-9 malignancy 135 measurement by xenon Blumgart, Herrmann 1 malignancy staging 135 clearance 88 Body metahohe hone disease of organ 363 tonicity disturbance 386 144-5 Blood pool wasting 384-5 normal132 gated studies 421, 590 Body composition 383 osteoarthritis 150 radiopharmaceuticals 27 age 384 osteoporosis 145 time-activity curves 362, 363 common patterns 384-7 Paget' s disease 145-7 tomography 16 hypotonicity 386-7 pattern recognition 133-4 venogram 81-2 inflammatory disease 385-6 primary hone tumours 144 Blood pool imaging 1-2, 4-17 injury 385-6 response to therapy clinical applications 10-16 obesity 384 assessment 135, 137 equilibrium-gated 4-9 race 384 rheumatoid arthritis 149 644 Index

Bone scan- cont'd. normal170, 172 Burkitt's Iymphoma 427 single photon emission static 170 Burn scars 427 computed tomographic stroke 176 scanning (SPECT) 151-2, 153 Brain tumour 174, 175, 186 C cell hyperplasia 433 skull133 positron emission tomography 11C-acetate three-phase 132-3, 460-516 (PET) 510 clearance 32-3 tracer uptake 145, 149, 153 Breast PET33 trauma 150 feeding 440-1 11C-labelled deoxyglucose 526 Bone tumours 442-5 milk radioactivity excretion 11C-labelled methionine 510, 521 chondrosarcoma 443 533-6 11C-labelled N-methylspiperone Ewing sarcoma 443 screening 568 510 multiple myeloma 443 Breast cancer 426, 427, 440-1 11C-labelled thymidine 451 osteogenic sarcoma 442-5 epidemiology 440-1 11C-methyl spiperone 192 primary 144 familial factors 441 11C-palmitate skeletal metastases 443-6 hormone dependence 427 clearance in patients with Bone-seeking agents, soft tissue internal mammary lymph cardiomyopathy 33 uptake 152-4 node metastases 506 PET33 Bousfield, G., 41 management 441 11C-raclopride, 192 76Br-spiperone 192 membrane-stable antigen in 14C Brain therapy 523 breath test 302 anatomy and physiology 158, metastases 441, 442, 445 glycine-labelled bile salt 302 160 oestrogen in 427 Iactose breath test 309 capillaries 158 oestrogen receptors 441 14C-labelled glycoholic acid tests capillary wall carrier systems PET receptor imaging 510 302, 308 158 racial factors 440 14C-labelled Iactose breath test death 160 radioimmunoscintigraphy in 302 distribution of vessels 159 496 I4C-labelled triolein 301, 309 glioma 496 radionuclide imaging 441-2 14C-labelled urea 302 layers around 159, 160 Breast carcinoma 327 c-myc oncogene 522 metastases in thyroid cancer antibody uptake 485 Caisson disease 150 224 bone metastases 135, 136-7, Calcitonin metastatic spread 429 138-9, 139, 140, 142, 143 Ievels in medullary thyroid neoplasms 173-6 clinical staging 139, 143 carcinoma 226 radiopharmaceuticals for 160-1 heart failure 15 measurement 219 resistance to flow 160 hepatic metastases 154 measurement after space occupying lesions 172 metastases 429 thyroidectomy 226 tracers 161 British Medical Journal 578 screening of relatives 227 uptake of HIPDM and IMP 163 Bronchitis, chronic Calculous disease 114-15 vascular territories 160 clinical symptoms 63 Calyces, dilated 118 133Xe washout technique 188-9 irreversible airways Campylobacter pylori 302 Brain imaging 524-81 obstruction 62 Cancer cerebral blood flow 524-80 Bronchopulmonary segments hereditary factors 427 metabolism indicators 526-7 47 localization by radiolabelled receptors 527 Bronchovascular unit 47 antibodies 521 static rectilinear 175 Bronchus squamous carcinoma risk of fatal 617 Brain scan 158, 597 437 staging abnormal172-3 Brown tumour 145 radioimmunoscintigraphy in chronic subdural haematoma Bruce, R. A. 41 494 176-7 Buccal mucosa squamous treatment and PET imaging CT scanning comparison 175 carcinoma 463 509 dynamic 171 Budd-Chiari syndrome 330 Cancerous tissue properties 521 false-positive 178 ascites 336 Captopril 92, 93 Index 645

test in renovascular disorder Catheterization of children 418 radiopharmaceuticals 191, 191 107-8 Cathode-ray tube 555 Cerebrovascular accident 160 Carbimazole 208, 230 Cavernous haemangioma 76 SPECT/BBB scan 177 Carcinoembryonic antigen (CEA) CBF radiopharmaceuticals 162-9 Cerebrovascular disease 482 intracellular distribution in rat blood-brain barrier scan 176 colorectal cancer staging 495 brains 167 cross-cerebellar diaschisis 180 Carcinogenesis mechanisms 620 99mTc-labelled ECD 167, 168, dementia 186 Carcinogens 327, 620 169 haemodynamic assessment 181 skin cancer 439 201Tl-labelled PET imaging 509 Carcinoma of the bronchus diethyldithiocarbamate Cervical carcinoma 427 chronic airway obstruction 61 (DDC) 166-7 Characteristic curves of diagnosis 61 Celllabelling 527-8 diagnostic methods 575-6 incidence 61 Central nervous system tumours Chemodectoma 433, 448 perfusion scanning 61 429-31 Chernobyl 620 radionuclide imaging 60-2 gliomas 429-30 Chest pain, non-cardiac 293-4 Carcinoma and metastatic spread intracranial metastases 430-1 Child abuse 400 428 meningiomas 430 Children Cardiac disease with posterior fossa tumours 430 interaction with 390 thrombophlebitis as Cerebra! abscess 178 sedation 390-1 complication 77 Cerebra! blood flow (CBF) 161, Chloramine T technique 488 Cardiac function monitaring 162 Chloride pump see Active with non-imaging nuclear autoregulation 185 non-ATPase-independent probe 16 brain tumour 186 sodium pump Cardiac gated studies 556 and cortical atrophy 179 Cholangiocarcinoma 439 Cardiac myosin 26 in epilepsy 186 Cholangiography 324 Cardiac output 3 grey matter values 180 Cholecystitis 324 intravenous injection of 1231-4-iodoantipyrine acute 334-5 monovalent cations 18 monitaring 162 Choledocal cyst 401 Cardiac tumour blood pool 1231-labelled amines 162-4 Choledocholithiasis 335 imaging 15 imaging 524-480 Cholestasis 332 Cardioembryonic antigen 522 measurement 188-90 intrahepatic 332-4 Cardiology sturlies 552 in migraine 186 Cholesterol 272 Cardiomyopathy 1, 33 routine measurement in man Cholestyramine 303, 304 blood pool imaging 14, 15 188 Chondrosarcoma 443 hypertrophic 13 99mTc-labelled HMPAO 164, Chordae tendinae 2 idiopathic 14 166 Chorion carcinoma 497 nc-palmitate clearance 33 99MTc-labelled PnAO 164, 166 Chrome ore industry 437 Cardiotoxicity 14 133Xe study, 178-9 Chromogranins 281 Cardiovascular imaging 522-4 Cerebra! blood volume (CBV) Chronic airway obstruction in Cardiovascular nuclear medicine 161, 162 lung cancer 61 1 Cerebra! focal ischaemia 166 Chronic obstructive airways Carnitine transferase deficiency Cerebra! haemorrhage with disease 50, 53, 62-4 33 99mTc-labelled ECD 169 radionuclide imaging 63-5 Carotid to brain transit time 170 Cerebra! muscarinic wash-out imaging 59 Carvical carcinoma 496 acetylcholine receptors 527 Cigarette smoke, 99MTc-labelled Catechol-o-methyltransferase Cerebral oedema in intracranial DTP A aerosol clearance 65 (COMT) 281 tumour 429 Cigarette smoking 48, 436-7 Catecholamines 280-1 Cerebraspinal fluid 191-2 Chronic airway obstruction output in phaeochromocytoma disorders in children 413 61 286 diversionary shunts 415, 417 chronic bronchitis 63 secretion from neuroblastoma leakage 192, 415 emphysema, 63 287 protein electrophoresis 192 Cimetidine 406 646 Index

Cirrhosis 330, 331 (CEA) in staging 495 time-activity curves 554 ascites 336 ll1Jn-labelled anti-CEA in 492 Congenital adrenal hyperplasia familial disorders 336 locally secreted antigen 482 278 hepatoma incidence 439, 440 membrane-stable antigen in Congenital arteriovenous primary liver cell cancer 427 therapy 523 malformation 88 Cisternogram 596 metastases 494 Congenital heart disease 418 studies in children 413 prognosis 496 Congenitallung abnormality Clinical benefit measurement of radioimmunoscintigraphy 66-7 diagnostic tests 578-81 495-6 Congenitally small kidney 107 case studies 581 Commando procedure 516 Congestive heart failure 13 clinical impact on management Common bile duct obstruction Conn' s syndrome see 579 334 Hyperaldosteronism, consensus evaluation 580 Common iliac vein obstruction primary databases 580-1 80 Consensus conference evaluation epidemiology 581 Compartmental models 95 580 mathematical modeHing 581 Competitive binding assay 242 Contrast meta-analysis 581 Compton scattering 542, 561 material risks 606 Clinical follow-up to diagnostic Computed tomography (CT) sialography 516 tests 584-5 abdominal sepsis 305 venography 78 Clinical practice consent forms abdominal trauma 315 Cor pulmonale blood pool 607-8 adrenal cortex 279 imaging 13 Clinical practice protocols 589, adrenal gland 271 Coronary artery 590-605 biliary tract 324 bypass surgery 32 Clinical value study design 580 bone tumours 442 stenosis and PET Clonidine 281 brain s~anning 158 measurement 32 14C02 breath tests 308-9 Cushing's syndrome 276 surgery 422 11 C02 tissue pH assessment 451 hearing disorders 518 Coronary artery disease S7Co-labelled bleomycin 521 intracerebral tumours 430 blood pool imaging in 57Co-labelled cyanocobalamin jaundice 333 diagnosis and evaluation 355 liver 321-2 10-11 57Co-labelled vitamin B12 255 liver size 326 diagnosis 23-4 58Co-labelled vitamin B12 307 nymph node scanning 503 PET measurement 31-2 vitamin B12 malabsorption 303 meningiomas 430 phase-analysis image 8 Coal workers 67 neuroblastoma 287 positron emission tomography Coeliac disease 339 parathyroid glands 267 (PET) 512 Cohort labelling 350 phaeochromocytoma imaging pre-test likelihood 45 Collimator 543-4, 556-7 436 sensitivity and specificity of data 557 primary hyperaldosteronism diagnostic tests 44 mechanical protection for 277-9 thallium imaging 22-3 camera 560 renal mass lesion 120 Coronary heart disease 1 testing 560 scale for usefulness 580 Cortical nodular hyperplasia 274 uniformity checking 561-2, 563 skin tumours 439 Cortisol 271 Colloid lymphoscintigraphy 494 Computer system 553-4 secretion in Cushing' s Colon cancer annual checks 564 syndrome 27 4 radioimmunotherapy 498 array processors 554 Cost-benefit analysis (CBA) 582 Colonic carcinoma 326 choice 557-8 Cost-effectiveness analysis (CEA) Colonic polyps 296 data storage matrix 553-4 582 Colonoscopy 296 dynamic images 556 Costing of new technology 581-2 Colorectal bleeding 296 noise 558 Costs of diagnostic methods 569 Colorectal cancer patient database 558 Council on Science and Society antibody uptake 485 pixel count 553, 555 report (1983) 568 carcinoembryonic antigen service contract 564 11 C-palmitate, 32 Index 647

SlCr platelet labelling 361 painful goitre 217 concordance with histology S1Cr-labelled chloride technique De-differentiation antigens 522 584 in protein-losing Decision aids 583 control583 enteropathy, 303, 308 Deconvolution analysis 95-6, decision aids 583 S1Cr-labelled chromate 556 disease prevalence 584 measurement of mean red Deep vein thrombosis 80, 80-3, education 583 celllife span (MRCLS) 350-2 369-70, 372 errors associated with SlCr-labelled chromate red cell blood pool venogram 82 measuring performance technique for Dehydroepiandrosterone 583-4 gastrointestinal bleeding 297 (DHEA) 271 ethical factors 585 51 Cr-labelled EDTA/technetium Dehydroepiandrosterone exclusion of data 584 MDP ratio 152 sulphate (DHEA-5) 272, 278, feedback of information 583 51Cr-labelled 280 financial incentives 583 ethylenediaminepenta• Dementia 158 goals 569 acetate (EDT A) blood-brain barrier scan 186-7 health costs 577 measurement of kidney clinical rating 187 image reading 584 excretion 91 multi-infarct 181, 182, 186 implementation of changes 583 SlCr-labelled red cells 347 positron emission tomography inter- and intra-observer bleeding 307 (PET) 510-11 variations 583-4 compatibility tests 353 toxic 186 logistic problems 585 red cell destruction sites 352-3 133Xe CBF study 179 non-matched controls 584 Creatinine excretion 281 Desoxycorticosterone excess 276 patient outcome 578 Cricoarytenoid joints 468 Detector pulse height energy prospective measurement of Crohn' s disease 304, 305 spectra 561 clinical impact on de-differentiation antigens 522 245-detector system 178 management 579-80 folate deficiency 355 Dexamethasone 27 4 publication bias 585 131 Cs 18, 256 Diabetes 387 random order 585 Cushing's syndrome 274-76, 436 Diabetic nephropathy 120 reference standards 584 adrenocortical scintigraphy Diagnosis, early 577 reporting 585 275, 276 Diagnostic accuracy 570-5 sample size 584 clinical features 274 false-negatives 570-2 statistical calculations 585 comuted tomography (CT) 276 false-positives 570-2 therapeutic impact 578 radiocholesterol uptake 274, predictive accuracy 573-4 Diaphragmatic lesions 340 275 receiver-operated characteristic Diarrhoea 303-4 Cutaneous malignant melanoma curve 575-6 alactasia 302 lymphoscintigraphy 507 sensitivity and specificity Diastolic volume 421 Cutaneous ulcers, chronic 86, 87, 572-3, 574 Diazepam 390 88 typical characteristic curve Dicopac test 303, 308, 355 Cyanotic heart disease 418 575-6 Diethyldithiocarbamate (DDC) Cystic fibrosis 66-7 Diagnostic clinical trial 578-9 164 133Xe clearance 66 Diagnostic evaluation trials 579 Diethylenetriaminepentaacetic Cystography, radionuclide 412 Diagnostic impact of methods acid (DTP A) 110, 488 576-8 Differential renal function Dacron grafts 370 Diagnostic method evaluation analysis 409, 412 Data display and processing 568 Digital subtraction angiography 504-6 Diagnostic nuclear medicine 53 dynamic images 556 radiation dose 620 parathyroid glands 267 heated object spectrum 555 Diagnostic tests Dihydrophenylalanine (dopa) 281 static images 554-6 benefits 577-8 Dihydroxymandelic acid 281 Databases 580-1 clinical benefit measurement Diphosphonate de Quervain's thyroiditis 202, 578-81 hone clearance 152 204, 219 clinical follow-up 584-5 uptake of hone 152 648 Index

Dipyridamole 18, 23 Dynamic renal scan 594 Epidemiology 581 contraindications 23 Dynodes 542 Epigastric fullness 299-300 thallium imaging 23 Dyshormonogenesis, iodide Epilepsy 158, 167 Disease transport abnormality 220 blood-brain barrier scan 186 prevalence 572, 584 CBF/CBV ratio alteration 167 prognosis 568 Early ischaemia 158 intracranial tumour 429 response to treatment 568 Echocardiography, 418 positron emission tomography staging 568 Ectopic ACTH syndrome 274 (PET) 511 threshold in populations 570, Ectopic thyroid 220-21, 222 Epithelial chronic inflammatory 571 Effective dose equivalent 607, conditions 427 Diskitis-osteomyelitis 396 610, 613 Epstein-Barr virus 427 Display system checking 560 pregnant women 607 Equilibrium Disproportionale upper septal Effective hepatic blood flow 320 blood pool imaging 421 thickening (DUST) 15 Effective renal plasma flow dialysis 240 Diuresis 387 (ERPF) 91, 101 Equilibrium-gated blood pool Dixels 556 Effusion fraction, left ventricular imaging Dopamine 281, 287 17 analysis 6-9 D2 receptors 192-3 Ejection fraction 3, 421 data collection 4-5, 6 receptor studies 192 calculation by first-pass blood Ejection fraction measurement Dopplerultrasound 75, 78 pool imaging 10 6-7 combined with radionuclide images 7 image recording 5-6 venography 85 magrtitude and disease 10 phase analysis 7-9 Dose measurement 4, 6-7 radiopharmaceutical 4 estimates 612-13 mitral regurgitation 14 ventricular volume calculation measurement 611-12 prognostic value 13 7 Dose assessment 610-13 right ventricular in cor Equipment dose estimates 612-13 pulmonale 13 annual checks 563-4 macroscopic dose from Elderly sick patient T3 and T4 choice 556-8, 557-8 internal emitter Ievels 203 daily checks 560-2 measurement 611-12 Electroencephalography 511 quality control 560 Dose-response curves 615-6 ß-emission 497, 498 service contracts 564 Dosimetry 609-10 Emission computer-assisted servicing 564-5 normal subjects 611 tomography (ECAT), testing 560 Doughnut sign 174, 174, 178 parathyroid imaging 261 weekly checks 562-4 Doxorubicin 14 Emission tomography Erythron 378 Drug-radiopharmaceutical instrumentation 549-51 Essential hypertension 103 incompatibility 533 Emphysema high renin 105 Dry mouth 293 clinical symptoms 63 Ethics of diagnostic trials 579, DTPA see irreversible airways 585 diethylenetriaminepenta• obstruction 62 Evaluation of diagnostic methods acetic acid End diastolic volume 568 Duchenne's muscular dystrophy measurement 4 cost-benefit analysis (CBA) 33 Endocrine tumours 433-6 582 Dumpingsyndrome 299, 300 adrenal tumours 435-6 cost-effectiveness analysis duodenal ulcer 298 anaplastic thyroid cancer 435 (CEA) 582 relapse 302 papillary carcinoma 433-4 costing 578, 581-2 duodenogastric reflux 300-1, parathyroid tumour 435 costs and benefits 569 600 thyroid 433 diagnostic accuracy 570-5 1,25-dyhydroxycholecalciferol Endoscopy in gastrointestinal diagnostic impact 576-8 254 bleeding 295 economic analyses 581 Dynamic equilibrium 240-2 Entamoeba histolytica 327 health risks 578 Dynamic images 556 Ependymoma 173 implementation of changes 583 Index 649

information required for costs Ferrokinetics 605 in AIDS scanning 65 and benefits 578 Ferrone monoclonal antibody 496 bronchogenic carcinoma methodology 568, 570-83 a-Fetoprotein 522 diagnosis 61 new technology 569-70 Fibrinogen, radio-iodine Iabelied hepatoma staging 447 optimal utilization 581-3 82 lung carcinoma staging 447 presentation of results 582-3 Fibrous dysplasia 442 Jung tumour location 438 technical capacity 570 Field of growth theory of malignant Iymphoma imaging techniques 570-83 neoplastic change 426 433 time factor 582 Film badge dosimeter 565 malignant myeloma metastasis Ewing's sarcoma 144, 443 Filtration fraction (FF) 92 imaging 447 Exercise Fine needle aspiration cytology 198 mediastinal disease imaging first-pass blood pool imaging 10 solitary nodules in goitre 219 447 imaging 512 solitary old nodule 214-15 melanoma avidity 447 Exercise electrocardiogram solitary thyroid nodule 205 parotid gland scan 463 testing 41-5 Finger clubbing 61 salivary gland imaging 516-7 analysis of results 43 First-pass blood pool imaging sarcoidosis disease activity 67 drugs 41 9-10 sarcoidosis scanning 518 end points 42 analysis 10 sinusitis imaging 465 equipment 41 gated scans 10 squamous carcinoma of head interpretation of results 44-5 injection technique 9-10 and neck imaging 431-2 maximal exercise protocols First-pass isotope angiogram 591 thyroid uptake 207 42-3 Flare response 137, 142 tuberculosis imaging 64 post-test probability 44 Flood field image 559 tumour imaging 446-7 predictive value 41 uniformity checking 561-2 uptake in multiple myeloma protocol41-2 Flow venogram 78, 80-1 443 Expiratory reserve volume 47 Foetus, antithyroid drugs 210 uptake prognostic indicator Folate deficiency in megoblastic 431 tsF scintigraphy in osteosarcoma anaemias 354, 355 whole body scan 605 443 Follicular carcinoma 222-23 67Ga-labelled citrate 335, 340 18F-labelled deoxyglucose 32, 521 Fourieranalysis 8, 9 67Ga-labelled gallium citrate tsF-labelled fluorodeoxyglucose Fractures, otolaryngeal466, 467 bone imaging 443 451, 510, 512, 526 Frame mode data collection of hepatoma imaging 440 18F-labelled fluoroestradiol 452 gated blood pool 4-5 Iymphoma imaging 463 18F-labelled oestradiol 510 Frusemide 94 uptake by cancer and 1BF-labelled uracil 47 active inflammatory tissue 521 tsF-labelled uridine 46 non-ATPase-independent 68Ga generator system 517 F(ab'h fragments 492 sodium pump inhibition 111 68Ga-labelled EDT A 451 Facial bone metastases 463 diuresis 111, 114 Gall bladder 321 Familial disorders 336 diuretic renography 110 cholangiography 324 Familial dyshormonogenesis 218 efficiency of output after Gallium imaging, mediastinal Fat (OF(t)) 112 400 absorption breath tests 301 renal response 97, 112 Gallstones 332 embolism 61 Functional imaging 556 Gamma camera 83, 84, 543-6 Fatty acids, radiolabelled 30, 524 Furosemide 409 air conditioning 558 52Fe chloride 378 Anger 164, 165, 181, 184, 59Fe 297 y-ray 543-4 chloride in bone marrow emission radiolabel 486 blood-brain barrier (BBB) scan imaging 378 energy of radionuclides 515 170 ferric chloride 356 pulse height spectrum 542, 543 bone scanning 131 ferric citrate 356 67Ga 255 computer sequence 170 ferrokinetics 357, 358, 359 abdominal abscess scanning Computersystem 553, 557-8 sites of distribution 358-60 304-5 dose measurement 611-12 650 Index

Gamma camera - cont' d blood loss measurement 601 Geiger counter 1 dual- or triple-channel pulse chronic 297-8 Generator systems for height analysis capability localization 600 radionuclides 517-8 557 Meckel' s diverticulum 296 Genitourinary problems in energy settings 561-2 occult 297 children 407-12 environment 558 Gastrointestinal problems in Germanium crystal 549 frusemide diuresis before renal children 400-7 Glioblastoma multiforme 430 radionuclide studies 111 biliary disease 401 Glioma 166 germanium crystal 549 gastro-oesophageal reflux 403 radioimmunotherapy 498 heat Ioad 558 liver disease 400-1, 401 Glomerular filtration imaging 593 image recording 557 pertechnate abdominal Glomerular filtration rate 91, 92, intrinsic resolution 563 imaging 403-7 101 mobile 547, 560 Gastrointestinal tract acute renal failure 116 multicrystal camera 547 abdominal infection and in children 409, 412 multiple energy windows 557 inflammation 304-5 stone obstruction 103 multiwire proportional counter anatomy 292 Glomerulonephritis 120 549 bacterial overgrowth of small Glomus jugulare tumours 433 in radioimmunoscintigraphy bowel302 Glottic carcinoma 431 491-2 Barrett's oesophagus detection Gloves 565 renal transplantation 126-7 306 Glucocorticoids 271 renovascular hypertension 105 bleeding 295-7 Glucose resolution check 562, 564 diarrhoea 299, 303-4 thallium loss from scanning cameras 547 dumping 299, 300 myocardium 19-20 service contract 564 epigastric fullness 299-300 uptake by cancerous tissue 521 spatial distortion checks 563 gastric emptying scanning Glucose metabolism specialized designs 547, 549 306-7 regional 511 thyroid scan 229 gastritis 300-1 and tumour proliferation rate uniformity check 561-2, 563 gastropulmonary aspiration 451 weight 558 scanning 306 Glycogen storage disease 336 GangHoneuroma 448 gut loss 301-3 Goitre Gas and coke industry 437 hypoproteinaemia 303 familial 220 Gastric acid secretion 293 malabsorption 301-3 intrathoracic 221 Gastric content aspiration 295 oesophageal pain 293-4 malignancy 218 Gastric emptying 292-3, 600 oesophageal reflux scanning nodular 206 radionuclide tests 300 305-6 painful217-18 rate 403 oesophageal transit 306 retrosternal 221 scanning 306-7 physiology 292-3 simple colloid 218-19 Gastric mucosa, ectopic 406 protein-losing enteropathy 303 simple multinodular 218-19 Gastric mucus secretion 293 recurrent ulceration 298-9 thyroid scan in assessment 218 Gastric stasis 299 salivary gland 294-5 Goitre, non-toxic 218-20 Gastric surgery salivary radioisotope scanning dyshormonogenesis 220 diarrhoea 299 305 investigation 218 duodenogastric reflux 300-1 scanning techniques 305-9 treatment 218 gastric stasis 299 steatorrhoea 301-2 Gold-195m (1 95mAu) 27-8, 517 Gastrin assay 298 upper gastrointestinal Graft patency 76 Gastrinoma 298 symptoms 301 Graft-versus-host disease 374 Gastritis 300-1 vitamin B12 malabsorption Granulocyte Gastro-oesophageal reflux 293, 302-3 destruction 376 599 vomiting 299-300 distribution 375 in children 403 Gastropulmonary aspiration kinetics 373-6 Gastrointestinal bleeding scanning 306 labeHing 372-3 acute 295-7 Gated blood pool scan 420-2, 590 pool374 Index 651

Graves' disease 203, 205 Hashitoxicosis 204 20IHg-labelled chlormerodrin 24 anti-TSH receptor antibodies HBsAg-positive sera 327 20 1Hg-labelled fluorescein 24 252 Health Physics 606 Hiatus hernia 297 antithyroglobulin and Health status 579 Hibernating myocardium 11 antimicrosomal antibodies Hearing disorders 518-9 High-performance liquid 252 Heart chromatography (HPLC) 481 choice of therapy 209 anatomy 2 Hiroshima 426 recurrence 221 beat 3 Hirsutism 278 thyroid stimulating antibodies blood vessels 2 His-Purkinje system 3 252 circulation 2-3 HIV antibody positivity 65 treatment 205, 208-9 oblique planes through 16 Hodgkin' s Iymphoma 335 Grey matter physiology 2-3 67Ga uptake 446 CBF values 180 positron emission tomography lymph node scan 504 SPECT imaging 181 (PET) 512 Homonymous hemanopia 170 Gut loss 301-3 rate 3 Hormone-dependent tumours Guttman Scale for the elderly 579 valves 2, 3 427 Heart, radionuclide imaging Hormone-free serum preparation 3H-folic acid 355 1-33 243 3H-oleic acid steatorrhoea test acquired heart disease 1 Hormones and neoplasia 427 301 cardiac function evaluation 1-2 Horner's syndrome 61, 217, 284 Haemangioendothelioma 439 Heat-damaged red blood cells Howell-Jolly bodies 336 Haemangioma 341 (HDRBC) in spienie imaging Human anti-mouse antibody hepatic 330 377 (HAMA) 482, 484 Haemangiosarcoma 439 Heated object spectrum 555 response 451 Haematology 346 Hemithyroidectomy 215, 223 Human choriogonadotrophin 522 blood volume 346-47 Heparin 53 Human immunodeficiency virus bone marrow imaging 378-9 Hepatitis 330 (HIV) 65 compatibility tests 353 and cholestasis 333 dementia 186 iron metabolism 355-60 neonatal 401 Human milk fat globule (HMFG) mean red celllife span Hepatoadenoma 330 522 (MRCLS) 350-2 Hepatobiliary disease 320 Huntington' s chorea 186 megoblastic anaemias 354-5 Hepatobiliary function 340-1 PET imaging 509 radiolabelled granulocytes 372-6 Hepatobiliary scan 602 Hurley' s tables 349 radiolabelled platelets 361-72 Hepatobiliary system Hyalinemembrane disease 48, red cell destruction sites 352-3 investigations 324, 325 66 spieen 376-8 Hepatoblastoma 400 99mTc-labelled DTP A aerosol Haematoma 385 Hepatocellular carcinoma 327, clearance 66 Haematopoietic system 378 328 Hybridoma 524 Haemochromatosis 336 Hepatocyte radiography 324 isolation 524 Haemolytic anaemia 52Fe image Hepatoma 338, 439 production 479 361 67Ga in staging 447imaging 440 selection 479, 481 Hamburger meat 204 radioimmunoscintigraphy in technology 613 Hashimoto' s thyroiditis 202, 212 497 Hydatid disease 329 antithyroglobulin and radioimmunotherapy 498 cysts 341 antimicrosomal antibodies 252 Hepatomegaly 324, 330-1 Hydrocephalus 190-1, 413 diagnosis 217 Hepatosplenomegaly 331 adult 191 family history 218 Herpes simplex virus 427 intracranial tumour 429 investigation and treatment Herpesvirus infection 65 Hydronephrosis 110 219-20 Hespan 362 17-hydroxyprogesterone painful goitre 217 Hexamethylpropyleneamine- (17-0HP) 278 perchlorate discharge test 220, oxime (HMP AO), 163 Hyperaemia 86 230 I97Hg-labelled chlormerodrin 521 Hyperaldosteronism 273 652 Index

Hyperaldosteronism, primary, post-parturn 252 lymphoscintigraphy 507 276-8 prevalence 198 monoclonal antibody labelling adrenocortical scan 276-7 relapse prediction 211 529 computed tomography 277-8 subacute thyroiditis 207 oral administration for dexamethasone-suppressible T3 and T4levels 199 parathyroid imaging 260, 277 therapy 200-1 261 radiocholesterol uptake 276 therapy for adults 209 painful goitre scan 217 Hyperaldosteronism, secondary therapy for children and radioiodine uptake test 230 276 adolescents 209 thyroid disease investigation Hyperandrogenism see Virilism therapy in pregnancy and 198 Hypercalcaemia 262 Iactation 209-10 thyroid scan 228, 229 skeletal 135, 140 thyroid hormones in 251 123!-labelled 4-iodoantipyrine 162 Hypernephroma 428, 445 transient neonatal 252 123!-labelled amines 162-4 Hyperostosis frontalis 133 treatment 207-13 1231-labelled fibrinogen 83 Hyperparathyroidism 145, 254, TRH Stimulation test 200 123!-labelled hexadecanoic acid 30 255 TSH measurement 200 123!-labelled HIPDM 163, 525 clinical features 255 Hypertonicity 387 123!-labelled hippuran for chronic diagnosis 255 Hypertrophie pulmonary renal failure 120 management 255 osteoarthropathy (HPO) 144 123!-labelled HMFG2 483 primary 255, 262, 267 Hypocalcaemia 255 ovarian adenocarcinoma renal264 Hypoproteinaemia 303 uptake 483 secondary 255, 262, 264, 267 Hypothalamic pituitary function in ovarian cancer 492 thallium/technetium scanning 250 123!-labelled IMP 163 technique 262 Hypothyroidism acute strake study 165 Hypertension 1, 104-09 clinical treatment 201-3 CBF scan 180 captopril test 107-8 congenital222 cerebral perfusion imaging 526 congenitally small kidney 107 neonatal202-3, 221-22, 250 SPECT study 182 control184 permanent with anatomical 1231-labelled MIBG due to local ischaemia 115 defects 222 adrenal medullary tumour malignant 120 pituitary 202 imaging 436 mean parenchymal transit time prevalence 198 bone metastasis imaging 447-9 (MPTT) 107 T3 and T4levels 199 glomus jugulare tumours 433 phaeochromocytoma 281 thyroid hormones in 202, 251 neuroblastoma uptake 448 renal arteriography 109 transient 202, 252 neuroectodermally derived renovascular 105 treatment 202 tumours 448 treatment 104 TSH assay 249-50 123!-labelled OIH 98, 103 Hyperthyroidism 203-213 TSH and T4 measurements 201 1231-Iabelied antithyroid drugs 201 Hypotonicity 386-7 3-quin uclidinyl-4-iodoben• associated with excess iodide Hypoxanthine 479 zilate (QNB) 527 212 Hypoxanthine 125! associated with excess thyroid guaninephosphoribosyl Iabaratory usage 243 hormone 212-3 transferase (HGPRT) 479 staff protection for handling associated with thyroid cancer 565 213 123! thyroid image 266 TSH immunometric assay 236 block/replacement regime 201 1231-IBZM 193-4 125!-labelled fibrinogen 83 causes 203 123I/131I-MIBG 30-1 125!-labelled fibrinogen thrombus choice of therapy 209-10 123! localization 593 clinical diagnosis 204 ectopic thyroid scan 221 125!-labelled human serum diagnosis 203, 207-8 evaluation of functioning hot albumin 347, 348 in the elderly 210 nodule 215-16 1251-labelled T3 243 intrauterine 252 immunoscintigraphy 450 125!-labelled T4 243 multinodular goitre 219 intrathoracic goitre scan 221 125!-labelled TSH 237, 238 Index 653

127I 131I-labelled macro-aggregated Ileal malabsorption of bile salts evaluation of solitary cold albumin 17 303,304 nodule 215 131I-labelled melanoma antibody Image functioning hot nodule 216 453 distortion in 131 I 1311-labelled MIBG 198, 282, 284, radioimmunoscintigraphy ablation therapy 223 447-9 491 anti CEA 498 adrenal medullary tumour enhancement in false positives for thyroid imaging 436 radioimmunoscintigraphy cancer 224 adrenal medullary tumour 492-4 Graves' disease therapy 208 therapy 613 reading 584 209 bone metastasis imaging 447-9 recording of gated blood pool hepatic uptake 224 dosimetry 284, 285 5-6 immunoscintigraphy 449-50 glomus jugulare tumours 433 recording in paediatrics 391-2 intrathoracic goitre 221 liver metastasis therapy 530 Imaging devices 556-7, 557 labeHing technique 498-9 medullary thyroid carcinoma Immigrant children 301 monoclonal antibody labeHing 226, 227, 435 Immunoassay 237-9 529 mid-gut carcinoid tumour antigen-antibody interaction Plummer' s disease treatment uptake 448 241 211 neuroblastoma uptake 287, data-processing programmes radiation calculation and 448, 452 249 thyroid mass 210 neuroectodermally derived design 246-7 in radioimmunoscintigraphy tumours 448 isotope handling 249 488 phaeochromocytoma therapy Iabaratory requirements 249 radioiodine uptake test 230 530 Immunoassay control 247-9 therapeutic dose 224 phaeochromocytoma uptake binding of Iabel 248 therapy 530-1 447-8 external quality-control thyroglobulin as adjunct 225 radiopharmacology 284-7 samples 247 thyroid cancer scan 224 therapy 288 internal quality-control thyroid disorder treatment 613 thyroid medullary carcinoma samples 247 thyroid metastases scanning therapy 448, 530 on-going records of assay 224 tumour imaging 529 performance 247-9 thyroid scan 229 tumour uptake 288 precision profile 248-9 thyroid uptake 210-1 uptake inhibition 284 response curve gradient 248 uptake and Iithium 224-25 131I-labelled monoclonal 1mmunoassay, practice of 242-46 whole body scan 225 antibodies curve fitting 245 1311-labelled antibody 492 in malignant meningitis hook effect 245 1311-labelled antiferritin 498 therapy 453-60 Iabelied material 243-4 1311-labelled AUA1 498 therapeutic ratio 498 problems 245 131 I-labelled fibrinogen 84 therapy with 530 reagents 242, 245 131 I-labelled H17E2 543 in ovarian 131I-labelled OIH 98 103, 521, 522 separation systems 245-6 cancer therapy 498 131 I-labelled Rose Bengal333, specific antisera 244 131I-labelled hippuran 105 341 standards 242-3, 245 131I-labelled HMFG2 in ovarian 131I-labelled toluidine blue 256, Immunoradiometric assays cancer therapy 498 264 (IRMAs) 235, 237 131 I-labelled human serum 131I-labelled UJ13A monoclonal antibodies 244 albumin in plasma volume radioimmunoscintigraphy reagents 242 measurement 347 486, 487 Separation process 245 131 I-Iabelied 19-iodo-cholesterol IBZM 193-4 specific antisera 244 272 Idiopathic hypertrophic subaortic Immunosuppression 126 131I-labelled stenosis (IHSS) 15 111In 6ß-iodomethyl-19-nor• IgG antibody molecule 523 attachment to transferrin 340 cholesterol (NP-59) 272, 273 IgG-coated red cells 378 celllabelling 527, 528 654 Index

111In- cont'd. platelet destruction 368 Injury and body composition formulation to platelet imaging 369 385-6 radiopharmaceuticals 516 renal aHograft rejection 370 Inspiratory reserve volume 47 immunoscintigraphy 450 spieen time-activity curves Insulin 19-20 platelet labeHing 360, 361-2 365, 366 Intact nephron hypothesis 92, red ceH volume measurement 11 1In-labeHed pure granulocytes 101, 113 347, 348 374 Interna! emitters 611 uptake in liver 489 111In-labeHed transferrin in bone Interna! mammary lymph node 111 In-DTP A chelated Iabel in skin marrow imaging 379 metastases 506 tumour imaging 439 11 1In-labelled tropolonate 362 International Commission on 111 In-labeHed acetylactonate 373 granulocyte labelling 375 Radiation Protection (ICRP) 111In-labeHed anti-CEA in leucocyte labeHing 372 606 colorectal cancer 492 111 In-labeHed white ceHs in bone Interstitiallung disease 48 111 In-labeHed antimyosin Fab 26 infection scanning 148-9 99mTc-labelled DTP A aerosol 111 In-labeHed autologaus 111 In-oxine-labelled autologaus clearance 66 leucocytes in hepatic abscess leucocytes 340 Intracardiac prosthetic valves 367 335 113In IntraceHular tracers 611 111In-labeHed chloride in iron attachment to transferrin 340 Intracoronary injection 17-18 uptake imaging 361 radioaerosols 518, 519 Intracranial metastases 430-1 111 In-labeHed red cell volume measurement Intracranial tumour 429 diethylenetriaminepenta• 347,348 Intrarenal blood flow distribution acetic acid anti-carcino 113In-labeHed transferrin as 103-4 monoclonal antibody 62 plasma marker 348 Intrarenal function distribution 111In-labeHed DTPA 191 113min formulation to 114-16 antibody percentage binding radiopharmaceuticals 516 calculous disease 114-15 490 113min-labelled red cells in spienie congenital abnormalities 116 monoclonal antibody T101 in red ceH volume 377 hypertension due to local skin tumour imaging 439 nsin generator system 517 ischaemia 115 ventriculoatrial shunt 192 Indium labelling for pyelonephritic scarring 115 111In-labelled granulocytes 372, radioimmunoscintigraphy reflux nephrology 114 376 488-9 renallocalization 115 111In-labeHed leucocytes Industrial accidents 620 Intravenous urography (IVU) 100 inflammation imaging 372 Infarct avid imaging 2, 24-7 frusemide 111 intra-abdominal sepsis acute myocardial necrosis Inulin, kidney excretion 91 scanning 305 detection 24 Iodeogen technique 488 pancreatitis scanning 305 antimyosin 26-7 Iodide trapping 222 spieen activity 374 non-specific agents for 24-7 meta-Iodobenzylguanidine 111In-labeHed monoclonal SPECT imaging 25 (MIBG) antiborlies 83 Infection in children 394, 396, in neuroblastoma detection abdominal sepsis scan 309 398 and treatment 521 111 In-labeHed oxine in leucocyte Inferior vena cava therapy in labelling 372 obstruction 80 phaeochromocytoma 452 111 In-labelled P256 in thrombosis occlusion 407 tumour imaging 447-9 investigation 371 Inflammation imaging 372 Iodofibrinogen 83 111 In-labeHed platelets Inflammatory bowel disease 296 p-iodophenyl pentadecanoic acid arterial thrombus 370, 373 Inflammatory exudate 385 (IPPA) 30 deep vein thrombosis Information density 170 Ionising Radiations Regulations investigation 369-70 Inhaled foreign body imaging 66 (1985) 607 gamma camera image 364 Inhibitive immunoglobulins 222 Ionizing radiation 426 graft uptake 370 Injection 191Jr generator system left ventricular mural apparatus 391 517 thrombus 370 techniques for paediatrics 391 Iridium-191m 27, 517 Index 655

Iron ectopic 116 Kupffer cell sarcoma 439 absorption 355-6 extraction efficiency 91 Kuppfer cells 320 deficiency anaemia 297 force applied to 109 distribution 356 function in neonates 407 Labelied hormone analogue 240 metabolism 355-60 horseshoe 116, 154 Lactation uptake imaging 359, 361 hydronephrotic 409, 412 antithyroid drugs 210 utilization (RCU) 356, 358 imaging 521-2, 594 hyperthyroidism therapy 209 Irradiation 442 localization 115 Large muscle dynamic exercise Irritable bowel syndrome 303, mass lesions 120-1 5-6 305 normal post-operative 123 Laryngeallesion three-phase Islet cell tumours 448 obstruction 103 hone scanning 468 Isonitriles 28-9 osteodystrophy 145, 152 Laryngeal squamous carcinoma Ivory osteoma 400 outflow evaluation 110 432 output efficiency 97 Laryngeal tumours 431 Japanese A-bomb survivors 610 parenchyma 112-13 Lasix stresstest 409, 410-12, 412 exposure 613 parenchymal transit time 107 Law of mass action 241, 242 lifetime risk projections 618 pelvic 116 LD50 of radiation exposure 613 radiation-induced disease 605 radionuclide study 407 Left ventricular mural thrombus relative risk model 616 radiopharmaceuticals 97-100 370 somatic risk data 617 rejection 124-5 Legg-Perthes disease,392, 393, Jaundice 324, 332-4 relative contribution to total 394 diagnosis 332 function 100 Leucocyte labelling 372, 528 IDA radiopharmaceuticals 333 resistance to force applied to Leukaemia 426 neonatal333 109 en plaque 177 radiocolloid image 333 stones 110 Japanese data 617 Journal of the American Medical 99mTc-labelled diphosphonate risk 618 Association 579 uptake 153-4 Lifespan shortening 620 Juxtaglomerular apparatus 92, 93 transit time 94, 97 Lifetime risk projections 618 transplant patients 412 Ligand binding assays 242 40K endogenous radioactivity 388 tubular function 91 Lindau-von Hippel disease 282 43K 18 tumour 110 Linear system models 95 Kaposi' s sarcoma 65 uptake and output Lipoprotein in atheroma Kamovsky index 579 components 96-7 detection 30 17-ketosteroids 278 81ml(r Lisbona, R. 81 Kidney administration 69 List mode data collection of abnormalities in abdominal availability 68 gated blood pool 5 trauma 317 comparison with ehest X-rays Lithium in 131I uptake 224-25 absolute measurement of 63 Li ver individual function 102-3 fans for dispersal 69 abnormal function tests 335-6 activity-time curve 96, 107 gas ventilation for abnormal platelet destruction allograft rejection 370 diaphragmatic lesions 340 368 anatomy and physiology 91 half-life 59, 68 abscess 327-9, 335 arteriography 109 lung fuction study 63 abscess localization 340 bilateral outflow obstruction lung ventilation radiotracing amoebic abscess 329 103 49 anatomy 320-1 carcinoma tracer uptake 444 regional perfusion 69 angiography 322 cardiac output to 412 regional ventilation images 72 blood-bome metastases 428 congenitally small 107 ventilation imaging 59, 518 cancer427 content curve 96 B1mKr in ventilation and carcinoid tumour 326 control system 110 perfusion imaging 59, 60 cysts 329, 330 contusion 316-17 Krypton-81m (B1mKr) 28 disease 330-1, 335-6 donors 122-3 Kultischitzy cells 437 disease in children 400-1, 401 656 Index

Liver- cont'd. Lumbar articular facet disease radiopharmaceuticals 518-9 disease progression 336, 153 ventilation 518-9 338-9 Lung Lung ventilation 47-8 enlargement 324, 326, 330-1 adenocarcinoma 437, 439 aerosol radiotracers 49 evaluation in abdominal anaplastic !arge cell carcinoma radiotracers 48-9 trauma 318 437 Luxury perfusion 185 fatty infiltration 330 anatomy 47 Lymph drainage of the lower focal disease 326-30 angiography and radionuclide limbs 504-6 focallesions 339-40 imaging 53 Lymph node scanning 503-7, 605 111In uptake 489 fluid exchange 48 agents used 503-4 investigations 323 metastases 224, 428, 429, 443 axillary node scanning 506-7 lesion vascularity 340 physiology 47 internal mammary lymph macrophage cell function radiotracers 48-9 nodes 506 impairment 330 regional perfusion 48 lymph nodes below the macrophages 320 scanning 47 diaphragm 504-6 metastases 326-7, 330, 338, secondary tumour spread 428 particle size 503 440,453 sequestration of pure radionuclide scan, 503 miscellaneous focallesions 330 granulocytes 367 Lymphangiectasis 303 needle biopsy 341 squamous carcinoma 436 Lymphangiography 503 palpation 324 studies and comparison of skin tumours 439 physiology 320 doses 612 Lymphangitis carcinomatosis 441 platelet destruction 364 tumours 436-9 Lymphatics and metastatic primary hepatic tumours 327 volume 47, 71 spread of tumour 428 radiocolloid techniques 324, Lung anaplastic small cell Lymphography 339-41 carcinoma see Oat cell radionuclide 507 response to surgery 338-9 carcinoma of lung X-ray 506 scan 601 Lung cancer Lymphoma 177, 433 sepsis 335 biopsy 438 children 400, 401 sepsis mortality 329 bone metastases 139 focal disease of spieen 331 shearing trauma 318 chronic airway obstruction 61 67Ga uptake 446 space occupying lesions 326 clinical presentation 437-9 67Ga gallium citrate imaging staging of malignancy 335 diagnosis 438 463 structure investigation 321-3 epidemiology 436-7 heart failure 15 trauma 336 management 438 radioimmunoscintigraphy in 497 tumours 327, 439-440 monoclonal antibody against radioimmunotherapy 498 venous obstruction 330 oncoprotein 522 Lymphoscintigraphy 503, 506 Localization receiver operating venous invasion 428 cutaneous malignant characteristic (LROC) X-ray 438 melanoma 507 analysis 556 Lung carcinoma new radioactive agents 507 Locomotor problems in children 67Ga in staging 447 392-4 gallium-67 imaging 61 Macroscopic dose from internal Loin pain 110 incidence 436 emitter measurement 611-12 Long-acting thyroid Stimulators positron imaging tomography MAG3 see Mercaptoacetyl (LATS) 252 62 triglycine Loop of Henle 93, 103 radioimmunoscintigraphy in Magnetic resonance imaging Low linear energy transfer 610 496 adrenal gland 271 Low-density Iipoprotein (LDL) 99mTc methylene consensus evaluation 579 272 diphosphonate (MDP) bone hearing disorders 518 Low-renin essential scanning 62 parathyroid glands 267 hypertension 276 thallium-201 chloride scanning Malabsorption, gastrointestinal 177Lu 255 62 301-3 Lugol's solution 289 Lung imaging vitamin B12 302-3, 304 Index 657

Malignant apudoma 285 osteoblastic lesion 516 Mineralocorticoids 271 Malignant melanoma sclerotic reaction 468 Miniature detectors 552 epidermal invasion 428 Meningitis, subdural177 Minimumtransit time (MinTT) lymphoscintigraphy 507 Meningomyelocoel 116 94 Malignant myeloma, 67Ga Menorrhagia 297 Misery perfusion 185 imaging 447 Menstrual disturbance 278 Mitral regurgitation 14 Malignant neoplasm, Mercaptoacetyl triglycine Mitral stenosis 14 three-phase bone scanning (MAG3) movement in Modified Bruce protocol 43 463-4 obstruction to outflow of Monoamine oxidase (MAO) 281 Malnutrition 301 kidney 110 Monoclonal antibody 524 Mammary lymphoscintigraphy Mercury-195m 517 binding affinity 481-2 441 Metabolie bone disease biological factors affecting Mammography 441, 568 99mTc-labelled uptake 482, 484 Mannitol94 diphosphonate uptake 152 cardiovascular imaging 524 Marine Lenhart syndrome 205-6 Metadrenaline 281 characterization 481-2 Maxillary antrim carcinoma 431 Metanephrine 280, 281 indium labelling 488-9, 490 Mean granulocyte life-span Metastases 428 isotype determination 481 (MGLS) 372, 376 adrenocortical tumours 436 labelling 528 Mean parenchymal transit time breast cancer 441, 442 patient allergy history 491 (MPTT) 94, 107, 109, 113 internal mammary lymph preparation 524-484 Mean platelet life-span (MPLS) node 506 purification 481 361, 364, 367 lung tumours 437 quality control 484-5 thrombocytopenia 369 osteoblastic activity 444, 446 radioiodine labelling 488 Mean red celllife span (MRCLS) osteogenic sarcoma 442-3 radiotherapy with 530 350-2 photopaenic 135 technetium labelling 489, 491 cohort labelling 350 radioimmunoscintigraphy in tumour imaging 449-51, 528-9 patterns of survival curves 352 location 494 tumour therapy 453-60, 613 random labelling 350 sites of spread 428-9 Monoclonal antisera 244 Meckel's diverticulum 292, 296, skeletal 443-6 Monoclonal gammopathies 426 299 Metastases, bone 135, 139, 441, Monovalent cation tracers 18 ectopic gastric mucosa 406 442 Mucosal neuroma syndrome 282 imaging 601 breast carcinoma 135, 136-7, Multichannel analyser 561 in infants 404-5 138-9, 139, 140, 142, 143 Multicrystal camera 9, 547 scanning 307 prostate carcinoma 135, 141, Multinodular goitre 216-17 Mediastinal venogram 593 143 Multiple endocrine neoplasia 282 Medullary thyroid carcinoma risk of fracture 137 Multiple gated blood pool scan 226-7, 434-5 Methimazole 208 590 diagnosis 226 Methionine 255 Multiple hit model 367 follow-up 226-7 beta-methyl p-iodophenyl Multiple myeloma 144, 443, 444 screening of relatives 227 pentadecanoic acid (BMIPP) Multiple primary tumours 426 surgical treatment 226-7 30 Myelofibrosis 359, 360 Megoblastic anaemias 354-5 Methylene blue 264 spienie red cell volume 377 folate deficiency 354, 355 MIBG see Myeloma 135, 524 vitamin 812 deficiency 354-5 meta-iodobenzylguanidine hybridoma preparation 479 Melanoma 335 Mickulicz's syndrome 517 Myocardial adrenergic receptors avidity for 67Ga 447 Microcirculation 85, 86 30-1 metastases 428, 429, 494 Micturating cystourogram 121 Myocardial imaging agents MIBG imaging 448 Mid-gut carcinoid tumour 448 525 monoclonal antibody therapy Migraine and blood-brain barrier Myocardial infarction 1, 522 453, 523 scan 185-6 acute 11-12 radioimmunoscintigraphy 496 Mills-Dornhorst technique blood pool imaging 11-12 Meningioma 173, 430 367 imaging 591 658 Index

Myocardial infarction- cont' d. Myofibrils 3 Neurofibroma, MIBG imaging left ventricular mural Myosin release 522 448 thrombus 370 Neurofibromatosis 282 sensitivity of 99mTc-PYP uptake 13N ammonia 522 Neurological problems in 25 Nadler's tables 349 children 413, 415, 417-18 thallium imaging 22-3 Nagasaki 426 cerebraspinal fluid disorders Myocardial ischaemia 1, 422 Nai(Tl) crystal 543, 545 413 blood pool imaging in Nai(TL) crystals, multicrystal CSF diversionary shunts 415, diagnosis and evaluation camera 547 417 10-11 a-Naphthylamine 427 CSF leaks 415 11 C-palmitate kinetics 32 ß-Naphthylamine 427 hydrocephalus 413 in newborn 422 National Institute for Biological Neuroreceptor studies 192-4 PET applications 33 Standards (UK) 243 Nevada weapons test site (Utah) segmental perfusion and National Pituitary Agency (USA) 617 exogenaus glucose 243 New technology introduction utilization mismatch 32 National Radiological Protedion 569-70 thallium scans 18-19 Board 619 New York Heart Association Myocardial metabolism Natural risk 617 Activity Scale 579 measurement 31-3 Nebulizers 518 13NH3PET studies 31 radiotracing 524 Needle biopsy 341 Nickel ore industry 437 Myocardial necrosis Nembutal391 Non-accidental injury of detection 24 Neonates, cyanotic 418 childhood 151 imaging with antimyosin Nephelometrie ADP platelet 363 Non-Hodgkin's Iymphoma 331, monoclonal antibodies 26 Nephron 332, 335 non-specific agents for autoregulatiori 113 67Ga uptake 446 imaging 24-7 cortical 92, 93, 94, 103, 104 Non-imaging nuclear probe Myocardial perfusion 161 cortical to juxtamedullary ratio 16-17 measurement of regional 103 Non-structural myocardial 17-18 juxtamedullary 93, 94, 103, 104 dysfunction of the newborn thallium scanning 422 Nephrotomography 271 422 Myocardial perfusion agents high-dose 120 Non-thrombotic emboli 60 28-30 Nephrotoxins 117 Noradrenaline 281 fatty acids and analogues 30 Nerve deafness 218 Normetadrenaline 281 metabolic agents 29-30 Neuroblastoma 166, 287-8 Nottingham health profile 579 99 mTc-labelled isonitriles 28-9 computed tomography (CT) Nuclear stethoscope 552 Myocardial perfusion imaging 287 Nutritional deficiency 301 in children 422-4 131I-labelled UJ13A planar 20 radioimmunoscintigraphy 150 2 tumour oxygen utilization sensitivity 23 486, 487 determination 451 specificity 23 131I-meta-iodobenzylguanidine Oat cell carcinoma of lung 428, Myocardial scanning with (MIBG) imaging 285, 286 436 thallium 422, 424 131 -meta-iodobenzylguanidineI heart failure 15 Myocarditis, 111In-labelled (MIBG) therapy 288 MIBG imaging 448 antimyosin Fab scanning 131 I-meta-iodobenzylguanidine Obstructing uropathy 111 26-7 (MIBG) uptake 287, 447-9 Obstmetion to outflow of kidney Myocardium 2 123I -meta-iodobenzylguanidine 109-12 contraction 3 (MIBG) uptake 448 antegrade perfusion pressure imaging 17 meta-iodobenzylguanidine measurement (APPM) routine imaging with gamma (MIBG) detection and 110-11 camera 18 treatment 521 pathology 110 thallium clearance 19, 20, radioimmunoscintigraphy 496 radiotracer movement 110 22 radioimmunotherapy 498 stone 110 Index 659

tumour 110 Osteomalacia 145, 146, 152 in radioimmunotherapy 499 ureteric contraction 110 Osteomyelitis 147, 148 therapy 530 Obstructive airways disease, complicating sinusitis 465 32P-labelled diisopropyl 99mTc-labelled aerosols 64 diagnosis in children 394, 396 fluorophosphonate (DFP) Obstructive hydrocephalus 414 frontal sinus 464 350 Obstructive nephropathy 109 sinuses 427 Paediatric cardiology 418, 420-4 Obstructive uropathy 109 three-phase bone scan 133 equilibrium blood pool Occupational exposure to Osteoporosis 145 imaging 420-2 radiation 613 Osteosarcoma 426 myocardial perfusion imaging Ocular melanoma, 99mTc-labelled ofbone 428 422-4 F(ab')z in 492 radioimmunoscintigraphy in radionuclide angiocardiogram Oesophagus 497 418, 420 dysmobility 294 Otolaryngology 460 shunt quantification 420 function 292 bony lesions 468, 516 Paediatrics 390 manometry 294 hearing disorders 518-9 child abuse 400 motility disorders 293-4 inflammatory lesions 464-66 child interaction 390 pain 293-4, 295 lacrimal drainage scanning gastrointestinal problems radionuclide transit studies 294 517-8 400-7 reflux disease 294 laryngeallesions 468 genitourinary problems 407-12 reflux scanning 305-6 salivary gland disease 516-7 image recording 391-2 transit studies 306, 599 temporamandibular pain infection 394, 397, 398 Oestrogen 427 467-8 injection techniques 391 thyroxine-binding globulin three-phase bone scanning locomotor problems 392-4 (TBG) Ievels 203 460-516 lung disease 66-7 OIH see Orthoiodohippurate trauma 466 mediastinal gallium imaging Oligodendroglioma 174 Otorhinorrhoea 415 400 Oliguria 116 Outflow obstruction atrophy 103 neurological problems 413, Oncogene 427, 522 Ovarian adenocarcinoma, 415, 417-18 Oncogene-antioncogene theory 1231-labelled HMFG2 uptake radiopharmaceutical dosage of cancer 522 483 391, 392 Oncogenic viruses, Ovarian cancer 530 seizures 418 tumour-producing 427 antibodies against 495 spondylosis 400 Oncoproteins 522 chemotherapy 495 Paget's disease 88, 134, 152, Oophorectomy 427 1231-labelled HMFG2 in 492 442 Opiate receptor studies 192 intraperitoneal bone osteosarcoma 427 Oral contraceptive pill273, 277, radioimmunotherapy 499 bone scan 145-7 327, 427 management 495 polyostotic 444 breast cancer 441 membrane-stable antigen in sclerotic changes 468 Orchidectomy 427 therapy 523 temporal bone 519 Organ activity determination 612 metastases 495, 614 Palladium-109 530 Orthoiodohippurate primary treatment 614 Pancreatitis 302 movement in obstruction to radioimmunoscintigraphy 494, 111ln-labelled leucocyte outflow of kidney 110 495,522 scanning 305 renal plasma flow radioimmunotherapy 498, Papillary carcinoma 222-23, measurement 91 613-14 433-4 Orthopaedic surgery 77 Ovary, polycystic 278 Paraaminohippurate (P AH), Osmium-191517 renal plasma flow Osteoarthritis bone scan 150 32p measurement 91 Osteoblast activity, 131, 139 difluorophosphonate-labelled Paraganglioma 448 Osteochondroma 442 granulocytes 374 1311-meta-iodobenzylguanidine Osteogenic sarcoma 144, 442-3 polycythaemia vera treatment (MIBG) imaging 285 Osteoidosteoma 144, 398-400 614 non-functioning 288 660 Index

Paranasal sinuses, inflammatory Patient chronic cutaneous ulcers 86 lesions 464-66 care evaluation 568 Peripheral vascular disease 75, 88 Parathormone (PTH) 254 diagnostic test benefits 577 applications of nuclear antibody 522 diagnostic test goals 569 medicine 76 in hyperparathyroidism 255 dosimetry 611 patient assessment 85 Parathyroid health costs of diagnostic tests radionuclide angiography 75-7 adenoma 255, 263, 264, 266, 578 Peristaisis 292 267 outcome in diagnostic tests 578 Pernicious anaemia 355 carcinoma 255, 262, 435 range in diagnostic test Pertechnate abdominal imaging hyperplasia 255 performance 584 in children 403-7 Parathyroid glands risk factors 609 Perthes' disease 150 anatomy 254 screening for disease 568 pH shift agents 526 arteriography 266 Patient Protedion Regulations Phaeochromocytoma 226, 281-4, CT scanning 267 566 436,437 digital subtraction 109Pd-labelled monoclonal bilateral 282 angiography 267 antibodies 498, 530 catecholamine output 286 ectopic 264 Peanut inhalation 66 131 I-meta-iodobenzylguanidine localizing abnormal 266, 267 Pelvic (MIBG) imaging 285, 447-8 localizing tests prior to surgery dilatation 110 131 I-meta-iodobenzylguanidine 267-8 transittime (PVTT) 94 (MIBG) therapy 288, 452, 530 magnetic resonance imaging Pendred's syndrome 218, 220 malignant 283 267 perchlorate discharge test 230 Pharyngeal tumours 431 physiology 254-5 Pentabarbital sodium 391 Phase analysis of gated blood re-operation 263, 267 Perchlorate discharge 230, 598 pool7-9 selective venous sampling 266 Percutaneous transhepatic Phenergan 391 uHrasound 266-7 cholangiography 333 Phenothiazinium dyes 264 Parathyroid scanning 254 Perfusion imaging 2, 17-24 Phenylethanolamine-N- current techniques 256-7 clinical problems 23-4 methyltransferase (PNMT) future developments 264-6 interpretation 21-2 281 history 255-6 intracoronary injection 17-18 Phlebitis 75 normal scan 258 intravenous injection 18 Photomultiplier tubes 542, 545 processing 257, 260-1 planar imaging 20 Anger camera 543 radionuclide localizing post-therapy testing 24 Photons 544 techniques 255-64 prognosis 24 Photopeak full width at half subtraction images 257, 259, single photon emission maximum 543, 545 260 computed tomography Pick's disease 166, 167, 186 tracer 264 (SPECT) 20 CBF abnormalities 179, 188 Parathyroidectomy, failed 262, Perfusion Jung scan 48, 51, 52, 591 SPECT imaging 181 264, 267 carcinoma of the bronchus 61 Piriform fossa carcinoma 431 Parenchymallung infection 64-5 radiopharmaceuticals in 69 Pitchblende 613 Parenchymal transit time index Perkardial effusion 1 Pituitary (PTTI) 94, 112-14 blood pool imaging 15, 16 adenoma PET 510 frusemide diuresis comparison Pericardium 2 tumours 173 114 Peripheral perfusion 593 Pixelcount 553, 555 obstruction nephropathy Peripheral perfusion assessment Placental alkaline phosphate presence or absence 110 85-8 (PLAP) 522 Parkinson's disease 186, 188 arteriovenous shunt Planar imaging 20, 180-1 dopamine receptor studies 193 measurements 88 thallium imaging 20-2 Parotid gland blood flow measurement by Plasma adenocarcinoma 463 xenon clearance 87-8 cell tumour 524 Iymphoma infiltration 463 capillary blockade and iron clearance (PIC) 356, 358 a-particle emitters 498 perfusion scanning 85-7 iron turnover (PIT) 356, 358 Index 661

renin activity (PRA) 276 hypertension 331-2 Promethazine 391 sodium Ievels 386 Positron emission tomography Propranolol 200, 208 Plasma volume 346-47, 603 (PET) 2, 31-3, 62, 452 contraindicated in pregnancy body wasting 385 brain metabolism scanning 511 210 measurement 347, 348-9 brain tumours 510 subacute thyroiditis treatment Plasma-cytoma 524 chemicallanguage of body 212 Plasmasteril 362 509-10 Propylthiouracil 208 Platelet clinical applications 509-12 Prostate cancer 497 destruction 364-5 data acquisition and analysis Prostate carcinoma 427 destruction identification 31 bone metastases 135, 141, 143 367-9 dementia 510-11 endocrine therapy 143 disposal sites 364 drug effects on receptors 509 B9Sr therapy 531 distribution 363-4, 365-7 epilepsy 511 Prosthetic valvular grafts 367, DP ratio 368 heart 512 370 imaging 369-72 instrumentation 549-51 Protein-losing enteropathy 303 kinetic disorders 365 Jung carcinoma 62 s1cr-chromium chloride kinetics 363-5 myocardial metabolism scanning 308 labeHing 361-3, 361-72, 528 measurement 32-3 Proximal tubule 93 life-span 364, 367 neuroreceptor studies 192 Pseudoanaemia 346 pool 363, 365-6 receptor site imaging 510 Pseudofractures 145, 146 production rate (PP) 369 regional chemistry Pseudopolycythaemia 346 survival curve 367 measurement 509-10 Psuedohyperaldosteronism 276 transittime 363, 365 regional perfusion Pulmonary artery pressure 48 viability 363 measurement 31 Pulmonary aspiration of gastric plethysmography 78 sensitivity 31 contents 295 combined with radionuclide stroke 510 Pulmonary blood flow 48 venography 85 tracer kinetic models 31 Pulmonary emboli 58 Plolycythaemia vera 613 for tumours 451-2 Pulmonary embolism 49-50, Plummer' s disease 204 Posterior fossa tumours 430 51-2, 53, 54, 55, 56, 57, 77 multinodular goitre 206 Potassium total body clinical features 50 radioiodine therapy 211 measurement 388 detection in patients with surgery 212 Predictive accuracy of diagnostic chronic obstructive airways thyroid scan 211 methods 573-4 disease 50, 53 treatment 211-2 Predictive value of tests 573-4 diagnosis with Pneumoconiosis 67 Prednisolone 212 ventilation-perfusion Pneumocystis carinii 66 Pregnancy imaging 50, 53 Pneumonectomy 61 hyperthyroidism therapy 209 diagnostic criteria 53 Pocket dose-rate meter 565 plasma volume 346 heparin treatment 53 Polya (Billroth II) gastrectomy radiation exposure 607 management 50 298, 299 T3 and T4levels 250-1 pathology 49-50 Polyclonal antibody 524 thyroid-stimulating antibody perfusion defects 53 Polycyclic hydrocarbons 427 measurement 252 probability rating 53 Polycystic thyroxine-binding globulin pulmonary angiography 53 disease 120 (TBG) Ievels 203 radiotracers in diagnosis 57, ovary syndrome 278 Press reporting of risks 609 59 Polycythaemia 184, 347 Primary liver cell cancer 427 Pulmonary epithelial Polyphosphates 519 Principal component analysis 94 permeability 48 Polyposis coli 426, 427 Principal components/factorial Pulmonary fibrosis 295 Porencephalic cyst 192 analysis 556 Pulmonary hypertension 14 Portal Prinzmetal, M. 1 Pyelonephritis 107, 120 fibrosis 330 Probability of causation 617 scarring 115 hepatis 321 Probe systems 552 Pyloroplasty 300 662 Index

Pyrexia of unknown origin 207, clinical studies 494-7 thyroid toxic nodule treatment 335 clinical use 494 205 colorectal cancer 496 uptake test 230 Q wave infarction 32 data analysis 491-4 Radiolabel choice for Q(t) measurement 119 in hepatoma 497 radioimmunoscintigraphy Quality-adjusted life year image distortion 491 486 (QAL Y) 582-3 image enhancement 492-4 Radiolabelied antibodies in image subtraction 493 cancer localization 519 R wave 4, 5 indiumlabeHing 488-9, 490 Radionuclide amplitude changes in exercise kinetic analysis 493 angiography 75-7, 460 ECG testing 43 labeHing efficiency 490 availability 515 Radiation in location of metatases 494 cyclotron-produced 515 background 610 in lung carcinoma 496 disposal 517 contamination monitors 565 in lymphoma 497 excretion 614 dose in diagnostic nuclear melanoma 496 formulation into medicine 620 in neuroblastoma 496 radiopharmaceuticals 516 dose-response curves 616-17 noise 485-6, 486 generator shielding 565 exposure levels 606 in osteosarcoma 497 generator systems 517-8 high dose wanted effects 613-14 ovarian cancer 495 half-life 485, 486, 515, 516, 614 hormesis 608 primary cancer staging 494 investigation 324 late unwanted effects 614-18 probability mapping 494 liver investigation 321 low dose rate hazard 616 quality control 484-5 oesophageal transit studies 294 occupational exposure 613 radioiodine labeHing 488 properties for medicinal use and pregnancy 607 radiolabet 485-6, 488-91 515-17 protection 565-6 re-evaluation of patient after therapy 530-1 protection bodies 610 surgery 494 in use 516 repair mechanisms 615 technetiumlabeHing 489, 491 venogram 592 risk coefficients 617-19 in thyroid carcinoma 496 Radiopharmaceuticals 2, 515 risk factor data 617 transparent film display 491-2 adverse reactions 531, 532, 533 risk perception 606 tumour markers in serum 494 biodistribution alterations 533 therapy 613 Radioimmunotherapy 497-9 biological testing 611 units 606 absorbed dose 497 bone imaging 519-21 Radiation-induced disease 615 benefit-risk ratio 613 brain imaging 524-481 Radioaerosols 518-9 bispecific antibody 499 for brain scanning 160-1 Radiocholesterol 289 dose assessment 497 breast feeding 533-6 Radiographie angiography, heterogeneity of intake 497 cardiovascular imaging 522-4 arterial anatomy 85 intraperitoneal technique celllabelling 527-8 Radiographie computed 498-9 complications in use 531-6 tomography 175, 175-6 iodine therapy 498 developments 518-483 chronic subdural haematoma ovarian cancer metastases 614 dose assessment 610 177 therapeutic ratio 498 drug incompatibility 533 head injury 179 uptake by normal tissue 497 kidney imaging 521-2 Radioimmunoassays (RIAs) 235, Radioiodinated albumin 1 lung imaging 518-9 237-9 Radioiodinated fatty acids myocardial perfusion agents reagents 242 524 28-30 separation process 245 Radioiodine new single-photon 27-30 Radioimmunoscintigraphy 521 elderly patient treatment 210 paediatric dosage 391, 392 absorbed radiation doses 488 labeHing for patient exposure 566 antibodies 523-4 radioimmunoscintigraphy positron-emitting 549 antigen 522-3 488 radionuclide therapy 530-1 in breast cancer 496 perchlorate discharge test 230 risks 606 clinical protocols 491-4 therapy 201 transport 565 Index 663

tumour imaging 528-9 Relative risk model 616 Respiratory distress syndrome Radiotherapy, radiation effects Renal artery stenosis 105, 106-7 418 613-14 Renal failure 116-120, 120, 264 Rest-exercise ventricular function Radium C 1 acute 116-17 studies 512 Radium dial painters 613 chronic 120 Restraint for children 390 81Rb 18 clinical and diagnostic Restrictive lung disease 67 186Re-labelled EHDP in bone evaluation 117-19 ventilation-perfusion ratio metastasis therapy 531 intravenous urography 117 67 Receiver operating characteristic uHrasound examination 117, 127Xe imaging 67 (ROC) 120 Retained gastricantrium analysis 556 Renal function syndrome (RGAS) 298 curve 575-6 absolute individual Reticuloendothelial system Rectal bleeding in infants 403 measurement 102 imaging 339, 378 Red cell measurement of individual platelet destruction 364 autologous 4 100-2 quantitative studies 339 destruction sites 352-3 radionuclide imaging 95 Reticulosarcoma, lymph node mass 603 studies in children 407-9, 412 scan 504-5 survival and sequestration 604 Renal impulse retention function Retinablastoma 427 utilization 358 113 Retroperitoneal air insufflation Red cell volume 346 Renal models 94-6 271 indium measurement 348 descriptive 94 Rhenium-186 530 measurement 347, 348 mathematical models 94-5 Rheumatic heart disease 1 sodium chromate physiological 94 Rheumatoid arthritis 149, 297, measurement 347 Renal plasma flow (RPF) 91, 92 516 spieen 377 Renal radionuclide investigations Rhinorrhoea 192, 415 99mTc-pertechnate 348 applications in clinical Rickets 301 Reference standards 584 problems 104-16 Risk Reflux nephrology 114 hypertension 104-9 assessment of hazards 621 Region of interest obstruction to outflow 109-12 factors 609-10 CBF measurement 190 relative renal function 112-16 one-in-a-million 620 dynamic images 556 Renaltransplantation 122-7 perception 619-20, 622 of kidney 100, 101 acute tubular necrosis 123-4 prediction 616 parenchymal 113 anuric 124 projection 613 Regional airways resistance 48 cadaver donor 122-3 of radiation exposure 619-20 Regional perfusion 69-70 extrarenal complications 126 Risk coefficients lung 48 extravasation of urine 125 changing values 618-19 measurement 31 live-related donor 122 data, 617 technique 69-70 obstruction 126 probability of causation, Regional ventilation perirenal collections 125-6 617-18 dynamic measurement 71-2 rejection 124-5 Ronchus, 61 81mKr images 72 vascular complications 126 Rosser and Kind health measurements 70-2 Renin 92 classification, 579 quasi-static measurement 70-1 output 109 Rubidium-82 myocardial blood radionuclide techniques 68-9 secretion 273 flow studies, 511-12 technique 69 Renogram 96 Regurgitant heart lesion 13 Renography 96 Sacroiliitis 149 Rejali, A. M. 1 diuretic 110 Salicylate 212 Relative renal function 112-16 probe 103, 105 Salivary gland 294-5 intrarenal function distribution Renovascular hypertension 93 disease 516-7, 518 114-16 Residual volume 47 function 516 parenchymal transit time index Resources and diagnostic scan 305, 599 (PTTI) 112-14 methods 569 Samarium-153, 530 664 Index

Sampie size for diagnostic tests Shunt quantification 420 Skin 584 left-to-right shunts 420 carcinoma 426 Sarcoidosis 48, 67-8, 517 right-to-left shunts 420 malignant change 439 disease activity assessment Shunt-function studies in metastases 429 with 67Ga 67-8 children 413 Skin cancer 426 gallium scanning 518 Sicca 295 diagnosis 439 99mTc-labelled DTP A aerosol Sickle cell anaemia 150 polycyclic hydrocarbons 427 clearance 65 Sickness impact profile 579 racial factors 439 133Xe clearance 67 Sigmoidoscopy 301 Skull Sarcomata 428 Single cell theory of neoplastic bone scan 133, 145 46Sc 256 change 426 fracture 160 Scalp 160 Single-photon emission fracture in infants 151 resistance to flow 160 computed tomography IS3Sm bone pain palliation 453 Scanning cameras 547 (SPECT) 20, 430, 597 Is3Sm-labelled EDTMP in Schillingtest 302, 303, 307-8, 604 abdominal trauma 317 metastatic bone cancer vitamin B12 deficiency 354-5 array processors 554 therapy 531 Schizophrenia, sulpiride therapy bone 151-2, 153, 462 Small cell carcinoma of the Jung 335 193 bone metastases 444 Small intestine Schwannoma 448 brain scanners 164 absorption 293 Scintadren 272 brain scanning 158 infection 302 Scintillation detectors 542-3 child patients 390 Sodium Scleroderma 301 chronic subdural haematoma body composition disturbance Screening programmes 582 177 386,387,388 Scurvy 301 computer.systems 553 dodecyl sulphate 75Se-labelled homocholic acid FWHM551 polyacrylamide gel 481 taurine (SeHCAT) in hearing disorders 518 iodide scintillators (Nai(Tl)) diarrhoea investigation infarct avid imaging 25 542 303-4 instrumentation 549-51 Sodium-potassium adenosine 75Se-labelled seleno-cholesterol liver metastatic disease 326 triphosphate system 18 436 Jung tumours 438, 439 Solitary cold nodule 214-15 75Se-labelled selenomethionine quantitative accuracy 550-1 hemithyroidectomy 215 256, 440 in radioimmunoscintigraphy Solitary thyroid nodules 213-17 75Se-labelled 6ß-selenomethyl-19- 492 cold 214-15 norcholesterol (SMC) 272, reconstruction algorithms 550 dominant cold nodule 216-17 273 skin tumours 439 functioning hot 215-16 Seattle Heart Watch study 42, 44 system checks 55, 63 investigation 214 Sedation 390-1 99mTc in imaging 29 malignancy 213, 215 Seizures in children 418 thallium imaging 22 multinodular goitre 216-17 ictal 418, 419 Single-photon emission Somatic cell hybridization 524 interictal418, 419 computed tomography Specificity of diagnostic methods Selenomethionine 296 (SPECT)/BBB scan in 572-3, 574 Seminoma 496 cerebrovascular accident Sphenoid wing meningioma 518 Sensitivity of diagnostic methods 176 Spinal cord transection 301 572-3, 574 Sino-atrial node 3 Spine, degenerative disease Septa! defect shunt 421 Sinusosteoma 516 150 Septic arthritis of the hip 394-5, Sinusitis Spironolactone 273, 277 394 acute 465 Spleen 321 Sequestered extracellular fluid chronic 466 blood cell pooling 377-8 385, 386 frontal464 congenital abnormalities 376 Serotonin receptor studies 192 Sipple' s syndrome 282 · disease 335-6 Shin splints 151 Sjogren's syndrome 295, 516 displacement 332 Short-range Auger electrons 611 Skeleton see Bone enlargement 331-2 Index 665

evaluation in abdominal fractures 151 macroaggregates in regional trauma 318 polycythaemia 347 perfusion 69-70 function investigation 341 pressure-volume curve during methylene diphosphonate granulocyte pooling 377 14 (MDP) bone scanning 62 haematology 376-8 Strake 1, 176 MIBI myocardial scan 590 hypofunction 336 CBF abnormality 167 myocardial clearance 29 imaging 376 positron emission tomography painful goitre scanning 217 infarction 335 (PET) 510 photon energy 29 platelet destruction 364, 368 prevention 184 red cell volume measurement platelet pooling 377 99mTc-labelled GH SPECT 176 347 red cell pooling 377 99mTc-labelled HMPAO rest-exercise ventricular scan 601, 602 scanning 166, 184 function studies 512 scanning in children 400, tomographic imaging (SPECT) reticuloendothelial imaging 402-3 181 339 shattered 402-3 Strake index 13 thyroid scan 210-1, 228, 229 time-activity curves 365, 366 Strake volume 3, 421 use 517 trauma 336 Stunned myocardium 12 99mTc Splenomegaly 331-2 Subarachnoid haemorrhage 160 hexamethylpropyleneamine blood volume measurement Subcutaneous sarcoma 426 oxime (HMP AO) 347 Subdural haematoma bone marrow imaging 379 platelet pool365, 366 blood-brain barrier scan 176-7 leucocyte labeHing 373 portal hypertension 331-2 dementia 186 small bowel imaging 374 sleen imaging 377 SPECT 176, 177 99mTc-DTPA, renal thrombocytopenia 369 Subdural haemorrhage, brain transplantation 122, 123, Spondylosis in children 400 scan 170 124, 126 Sports injuries 151 Subphrenic abscess 400, 404 99mTc-labelled aerosols in Squamous carcinoma Superior sagittal sinus obstructive airways disease of the head and neck 431-3 thrombosis 82 64 of the skin 426 Superscan of malignancy 135 99mTc-labelled albumin B9Sr Syringe shields 566 background subtraction 493 pain palliation in bone 99mTc-labelled albumin metastases 453 T3 see Triiodothyronine macroaggregate prostate carcinoma therapy 531 T4 see Thyroxine chronic foot ulcers 87 SSKI289 T-celllymphoma 439 liver metastasis imaging 440 ST segment changes in exercise Tamoxifen 427, 441 peripheral perfusion scanning ECG43 Tantalum-178 (1 78Ta) 28 85 Stannous reduction technique 81 99mTc 99mTc-labelled All Bran 305 Staphylococcal protein A 481 aerosols in ventilation imaging 99mTc-labelled antimony sulphide Static renal image 594 68 colloid 503 Statistical calculations for DTP A aerosols 68, 69 99mTc-labelled blood red cells, diagnostic tests 585 energy resolution checks 563 spienie red cell volume 377 Steatorrhoea 301-2 evaluation of functioning hot 99mTc-labelled idiopathic 355 nodule 215-16 carbomethoxyisopropyl Stein-Leventhal syndrome 278 evaluation of solitary cold isonitrile 523 Stellate ganglion blockade 284 nodule 215 99mTc-labelled carboxymethyl Stenosis, critical 184 formulation to isonitrile 28 Stilboestrol 427 radiopharmaceuticals 516 99mTc-labelled colloid liver Stoma eh in gastric emptying scanning imaging 440, 442 gastric acid secretion 293 306 99mTc-labelled colloid spleen gastric emptying 292-3 half-life 29 imaging 442 gastric mucus secretion 293 immunoscintigraphy 450 99mTc-labelled dicarboxypropane Stress injection schedule 29 diphosphonate (DPD) 520 666 Index

99mTc-labelled pathophysiology of bone 99mTc-labelled human serum diethyldithiocarbamate uptake 131 albumin 4 (DDC) 526 whole body measurement 152 hepatic lesion vascularity 340 99mTc-labelled 99mTc-labelled DI5IDA in biliary lung imaging 518 diethylenetriaminepenta• atresia 396, 397 99mTc-labelled acetic acid (DTPA) 9, 97-8, 99mTc-labelled DMPE 523 hydroxymethylenedi• 161 99mTc-labelled ECD 167, 168, 169 phosphonate (HMDP) 520 abdominal trauma 315 99mTc-labelled 99mTc-labelled iminodiacetic acid aerosols in alveolar clearance ethylene-hydroxydiphos• (IDA) 340 65 phonate 520 acute cholecystitis brain imaging 430, 524 99mTc-labelled F(ab'h investigation 335 cisternography in children 413 fragment of 225.285, 484 gall bladder imaging 321 gastric bleeding 297 melanoma hepatobiliary agents 338 hyaline membrane disease 66 radioimmunoscintigraphy hepatobiliary investigation 333 kidney excretion 91 496 neonatal jaundice investigation kidney imaging 521 in ocular melanoma 492 334 kidney output curve 96-7 99mTc-labelled fine carbon 99mTc-labelled isonitriles 28-9, 87 meningioma imaging 430 particles 49 99mTc-labelled macroaggregates with MIBG imaging 287 99mTc-labelled glucoheptonate 48 radioaerosols, 518, 519 24, 161, 409 aerosols 49 renal failure, 118, 120 brain imaging 430, 524 of albumin 17, 78, 80, 81 renal mass lesions 120 intracranial metastases 431 99mTc-labelled mercaptoacetyl renal parenchyma 119 meningioma imaging 430 triglycine (MAG3) 98-99, renal scanning in children 99mTc-labelled heat-damaged red 521-2 408-9 cells (HDRBC) clearance 102 renal transplants 122, 123, spienie imaging 377 renal failure 118, 119, 120 124 spienie red cell volume 377 renal plasma flow vesico-ureteric reflux 121-2 99mTc-labelled measurement 91 99mTc-labelled hexakis-t-butylisonitrile 99mTc-labelled 2-methoxy dimercaptosuccinate (TBI) 523 2-methylpropyl isonitrile 28 (DM5A) 100 99mTc-labelled 99mTc-labelled methoxyisobutyl absolute individual renal hexamethylpropyleneamine• isonitrile 523 function measurement 13 oxime (HMPAO) 164, 166, 99mTc-labelled congenital abnormalities of 168 methylenediphosphonate renal tract 116 abdominal sepsis scan 305 461, 520 kidney imaging 521 acute stroke demonstration 166 99mTc-labelled microspheres 48 medullary thyroid carcinoma acute stroke identification 184 diaphragmatic lesions 340 226 brain imaging 167, 526 reticuloendothelial imaging pyelonephritic scarring 115 brain tumour 186, 430 339 reflux nephrology 114 CBF 5PECT 181, 183, 186 right-to-left shunts 420 renal failure 118, 119, 120 distribution in dog brain 164, 99mTc-labelled monoclonal renallocalization 115 166 antibodies 489, 491 renal mass lesions 120 leucocyte labelling 527 99mTc-labelled 99mTc-labelled dimethylaminodi• migraine 185-6 N,N' -bis(mercaptoacet• phosphonate (DMAD) 520 platelet labelling 528 amido)-ethylenediamine 99mTc-labelled diphosphonate preparation 166 (DAD5) 521 152 radioimmunoscintigraphy 521 99mTc-labelled pentavalent bone metastasis imaging 444 seizure evaluation 418 dimercapto succinic acid bone scanning 131 structure 165 (VDM5A) 198 bone tumours 442, 443 99mTc-labelled HIDA bone metastasis imaging 446 kidney uptake 153-4 duodenogastric reflux 301 squamous carcinoma uptake local measurement in bone 152 radioaerosols 518 432 Index 667

thyroid carcinoma scanning Barrett' s oesophagus detection data recording 20 434 306 dipyridamole vasodilation 23 tumour imaging 449, 529 blood-brain barrier (BBB) scan lung clearance 21 99mTc-labelled phosphate 131, 170 myocardial scan 22, 590 161 brain imaging 430, 524 peripheral perfusion studies 85 99mTc-labelled phosphonates 161 brain neoplasms 173 planar imaging 21-2 99mTc-labelled plasmin 82, 84 compared with 1311 scan 225 recording equipment 20 99mTc-labelled PnAO 164, 166 CSF leakage 192 sensitivity 23 99mTc-labelled polyphosphate 519 evaluation of CSF diversionary sequence 21 99mTc-labelled porphyrin in shunts 415 single photon emission abdominal sepsis scan 305 false-positive scans 297 computed tomography 99mTc-labelled Pseudogas gastric bleeding 297 (SPECT) 22 ventilation imaging 59, 519 gastric emptying scanning stress-injected 23 99mTc-labelled pyrophosphate 306-7 Thallium-201 (99mTc-PYP) 24-5, 520 gastric mucosa uptake 299 chloride scanning 62 false positives 25 gastropulmonary aspiration exercise imaging 512 marker of severe injury 26 scanning 306 Thallium-activated caesium mechanism of uptake 24-5 lacrimal drainage scanning iodide detector 552 prognosis 25 517-8 Three Mile Island 620 time course and extent 25 Meckel' s diverticulum Three-phase bone scanning transmural infarcts 25 scanning 296, 307 460-516, 596 99mTc-labelled meningioma imaging 430 bony lesions 468, 516 radiopharmaceutical parathyroid carcinoma face 461-2 for angiography 75 imaging 435 inflammatory lesions 464-66 for cardiovascular imaging 523 parathyroid imaging 256 interpretation 461-2 99mTc-labelled red blood cells 76 radionuclide angiocardiogram laryngeallesions 468 brain tracing 162 420 malignant neoplasm 463-4 CBF measurement 190 red cell volume 348 temporomandibular pain drug effects 533 salivary gland scanning 294, 467-8 hepatic lesion vascularity 340 305, 516 trauma 466, 467 venogram 81, 83, 84 thyroid cancer scanning 225 Thrombocytopenia 366, 368 99mTc-labelled renography 370 thyroid imaging 228, 229, 433, interpretation 369 99mTc-labelled rhenium sulphur 434,435 platelet labeHing 362-3 radioaerosols 518 uptake in watershed infarction Thrombolytic therapy 99mTc-labelled sodium 176 acute myocardial salvage pertechnate 161 99mTc-Sesta MIBI 29, 264, 266 assessment 24 99mTc-labelled streptokinase 82 99mTc-stannous DTP A 127 wall motion abnormalities 99mTc-labelled sulphur colloid 9 Tear pump mechanism 517 12 abdominal abscess scan 304 Technical capacity of diagnostic Thrombophlebitis 75 gastric bleeding 297 methods 570 blood pool venogram 81-2 gastric content aspiration 295 Technigas 69 detection 77-85 liver tumour imaging 440 Temporal bone disease 518 diagnosis 77-8 oesophageal reflux scanning Temporamandibularjoint flow venogram 78, 80-1 305-6 arthritis 467 t2SJ-labelled fibrinogen oesophageal transit scanning disease 467-8 technique 83 306 pain and three-phase bone 1311-labelled fibrinogen spienie imaging 376 scanning 467-8 84 99mTc-labelled tetracycline 24 Tertiary butylisonitrile (TBI) 28 iodofibrinogen with external 99mTc-labelled tin colloid in liver Testosterone 278 counting techniques 83 tumour imaging 440 Thallium imaging 18-20 radio-iodine labelled 99 mTc-labelled urokinase 82 clinical applications 22-3 fibrinogen 82 99mTc-pertechnate 4, 68 computer image 21-2 thrombus localization 82-5 668 Index

Thrombus whole body scan 229-30, 598 Iigand binding assays 242 localization 82-5 Thyroid disease 198 rneasurernent in visualization with garnrna classification 199 hypothyroidisrn 201 carnera 83, 84 1311 treatrnent 613 rneasurernent in radioiodine Thyrnidine 479 radionuclides used in 228 treatrnent 201 Thyrnus 400 radiopharrnaceuticals 198 rneasurernent and thyroid Thyroglobulin 225 uHrasound roJe 214 function 240 Thyroid Thyroid dysfunction rnolecular weight 242 adenorna 265 clinical situations 200-3 neonatal assay, 250 anti-TSH receptor antibodies diagnosis 199-203 quality control sarnples for 252 pathophysiology 199-200 assay 247 autoantibodies 251-2 radioiodine uptake test, 230 receptors 252 beef 204 Thyroid function tests in vitro response to TRH test 228 blockade 288 227-8, 235 screening in neonatal carcinorna 204, 496 assay principles 235-6 hypothyroidisrn 202-3 ectopic 220-21, 222 irnrnunornetric assay systern thyroid status assessrnent 235 follicular carcinorna 428 235, 236 Thyroid stirnulating growth-stirnulating antibodies Thyroid horrnone horrnone-blocking 252 clinical applications of assays antibodies 252 irnaging in vivo 228-30 249-52 Thyroid turnours 433 lingual 220-21 excess 213 anaplastic 435 Iymphoma 219 free 239-40 classification 223 rnass 210 irnrnunoassays 235 rnedullary carcinorna 434-5 rnedullary carcinorna 448, 530 radioirnrnunoassays (RIAs) papillary carcinorna 433-4 rnetastases 213 239-40 TSH dependent 427 rnicrosornal autoantibodies 202 replacernent in Thyroidectorny rnonitoring 565 hypothyroidisrn 202 for rnedullary thyroid nodule 198, 204, 205, 217 Thyroid scan 210-1, 598 carcinorna 226 organification defects 230 in assessrnent of goitre 218 relatives of rnedullary thyroid radionuclide scan 228-9 before raioiodine therapy in carcinorna patients 227 stirnulating abnormal Plurnrner's disease 211 subtotal 201, 208-9 irnrnunoglobulin 203 solitary thyroid nodules 214 total223 stirnulating antibodies 252 Thyroid stirnulating horrnone Thyroiditis sublingual 220-21 (TSH) 200 acute supurative 217-18 sudden onset pain 217 antibody and antigen dynarnic painless 204 toxic nodule 205-6 equilibriurn 240-2 post-parturn 204, 207 Thyroid cancer 213, 222-27, 426 antibody binding sites 242 pyrexia of unknown origin brain rnetastases 224 assay 235-6, 247, 250 (PUO) 207 early disease rnanagernent block/replacernent regirne subacute 204, 207, 212, 217, 223-24 201 218 first-degree farnily screening clinical applications of assays Thyrotoxicosis 219 249-50 arniodarone-induced 207 mr scan 224 cornpetitive binding assay 242 cause 204-205 1311 therapy 452 hypothalarnic pituitary diagnosis and rnanagernent immediate treatrnent 224 function assay 250 204-207 rnetastases 224 irnrnunoassays 237-9 in the elderly 210 painful goitre 217 irnrnunornetric assay 236, 237 irnpalpable gland 206-7 radioirnrnunoscintigraphy in 496 irnrnunoradiornetric assay low tracer uptake 207 scanning techniques 225-6 (IRMA) 249 nodular goitre associated with thyroglobulin use 225 iodination 243, 244 206 treatrnent and follow-up Ievel in simple colloid or thyroid scan 204 222-25 rnultinodular goitre 219 treatrnent 198 Index 669

Thyrotropin-releasing hormone parathyroid uptake tomographic imaging (SPECT) (TRH) 200 mechanism 263 181 short test 228 radioimmunoscintigraphy 521 Transient myocardial ischaemia stimulation test 200, 202 thyroid cancer scanning 225 (TMI) 423, 424 test 227-8 tissue perfusion demonstration Trauma Thyroxine 85 bone scan 150-1 binding globulin (TBC) 2°1Tl-labelled chloride 161, 225 facial 466, 467 measurement 251 201 Tl-labelled hypertonicity 387 elderly sick patient Ievels 203 diethyldithiocarbamate occult fracture 151 excess medication 213 (DDC) 166-7 radionuclide imaging of spieen free hormone measurement 20ITJ-thallous chloride 256 and liver 336 250-1 Jung tumour imaging 438-9 shin splints 151, 151 free serum (fT4) 199 parathyroid carcinoma stress fractures 151 in hyperthyroidism 251 imaging435 three-phase bone scanning in hypothyroidism 201, 202, thyroid cancer imaging 449 466,467 251 tumour imaging 449, 529 Traumatic oedema 385 Ievels for antithyroid drug uptake by anaplastic thyroid Tricuspid valve disease 14 treatment 201 cancer 435 Triglyceride body stores 384 measurement in 20ITJf99mTc parathyroid imaging Triiodothyronine hypothyroidism 201 256, 256-64 assay 245 radioimmunoassays (RIAs) accuracy 262-4 blocklreplacement regime 201 239-40 false positives 264 elderly sick patient Ievels 203 replacement therapy 250 localization prior to surgery free hormone measurement screening in neonatal 268 250-1 hypothyroidism 202-3 problems 260 free serum (fT3) 199 therapy after surgery 209 TLD finger badge dosimeter in hyperthyroidism 251 Thyroxine-binding globulin 565 in hypothyroidism 251 (TBC) 200, 239 TNM system of staging 428 Ievels for antithyroid drug oestrogen therapy Ievels 203 Tobacco smoking see Cigarette treatment 201 pregnancy Ievels 203 smoking radioimmunoassays (RIAs) Thyroxine-binding prealbumin Toluidine blue 264 239-40 (TBPA) 239 Tomographie imaging (SPECT) Trixels 556 Time-activity curve 7 181, 183-4 Tropical sprue 355 analysis 8-9 Tongue carcinoma 431 True-negative results 571-2 Tinnitus, pulsatile 518 Total exchangeable potassium True-positive results 571-2 201Tl 18-20, 256 (TEK) 384, 385, 386, 388 Tuberculosis, 67Ca imaging 65 angiography for peripheral Total exchangeable sodium Tubuloglomerular balance 92, vascular disorders 75 (TENa) 384, 385, 386 113 evaluation of solitary cold Toxic adenoma 204 Tumour nodule 215 Toxic autonomous nodules see amino acid metabolism 451 functioning hot nodule 216 Plummer' s disease antibody uptake 482 half-life 18 Toxic diffuse goitre see Craves' blood spread 428 heart function imaging 512 disease blood supply 482 imaging characteristics 20 Toxic nodular goitre 204 bone 442-5 medullary thyroid carcinoma Transfer function 556 central nervous system 429-31 scan 226 Transferrio 340 chemical agents in myocardial blood flow studies Transient ischaemia 158 development 426 522 Transient ischaemic attack (TIA) emboli 428 myocardial clearance 19-20 167, 184-5 endocrine 433-6 myocardial scanning 422, cause 184 67Ca imaging 446-7 424 critical stenosis 184 glucose metabolism 451 parathyroid images 257 stroke pathology 184 hormone-dependent 427 670 Index

Tumour- cont'd. abdominal sepsis 305 Ventilation-perfusion imaging image subtraction in abdominal trauma 315 50, 53, 54, 59, 63, 64, 71-2 radioimmunoscintigraphy biliary tract 324 carcinoma of the bronchus 61 493 jaundice 333 effects on further management immunoscintigraphy 450 liver 321 56 invasion into lymphatics 428 lymph node scanning 503 management of patients 53, 56 kinetic analysis 482 renal failure 117, 120 pulmonary emboli mirnies 60 liver 439-40 renal mass lesion 120 repeat scan 56 Jung 436-9 solitary cold nodule 214 Yentriele markers in serum 494 Ultraviolet radiation 426 dilatation and mitral MIBG imaging 447-9 Unit MET protocol 43 regurgitation 14 monoclonal antibody imaging Uptake function 95 dysfunction 12, 14 449-51 Uraemia 301 failure and blood pool oxygen utilization 451 Ureter tomography 16 positron emission tomography contraction 94, 110 filling and emptying rate 4 (PET) 451-2, 510 obstruction in renal infarction and blood pool proliferation studies 451 transplantation 126 imaging 12 radiolabel uptake 493 Urinary concentration shunt patency 192 radiolabelled monoclonal counter-current hypothesis stroke volume 13 antiborlies 449 93 volume calculation 7 radionuclide labelling 449-50 Urinary free cortisol (UFC) 274 Ventricular function radionuclide targetting 613 Urinary tract transitional cell analysis 421-2 radiopharmaceutical therapy tumours 426 conduction abnormalities 3 452-3 Urine in coronary artery disease 11 radiosensitivity 497 flow rate 93 first-pass gated scans 10 sites of metastatic spread 428-9 residual volume 59-5 measurement 4, 10 staging 428 Urography 117 Ventriculoatrial shunt 415 99mTc-labelled V DMSA US NAS BEIR Committee 616 Ventriculoperitoneal shunt 415, imaging449 Uterine leiomyomata 426 416-17 therapeutic blocked 416-17 radiopharmaceuticals 453 Vaginal carcinoma, lymph node Vertebral collapse 147 2°1Tl-thallous chloride imaging scan 505 Vesico-ureteric reflux 121-2, 409, 449 Vagotomy 299, 300 595 viral associations 427 Valium 391 indirect method 121-2 Tumour imaging 426-7, 528-9 Valvular disease, blood pool retrograde method 122 monoclonal antiborlies 528-9 imaging 13 VEST 16-17 radioiodinated MIBG 529 Vanillylmandelic acid (VMA) Virilism 278-9 99mTc-labelled pentavalent 280, 281 DS adrenocortical scintigraphy dimercaptosuccinic acid (V Vanylmondelic acid, urinary 226 278 DMSA) 529 Varicose ulcers 427 Virus-related antigens 522 techniques 446-9 Varicose veins 88 Vitamin B12 zoiTJ-thallous chloride 529 Vascular insufficiency 87 absorption imaging 307-8, 604 Tumours of the head and neck Vascular trauma 76 metabolism investigation 551 431-3 Vegans 301 Vitamin B12 deficiency 301 glomus jugulare tumours 433 Venogram 593 megoblastic anaemias 354-5 Iymphomas 433 lower extremity patterns 80 Schilling test 354-5 Typical characteristic curve 575-6 Venous occlusion 75 Vitamin B12 malabsorption L-tyrosine 280 Ventilation imaging 592 302-3, 304 Tyrosinosis 336 agents 57, 59 Dicopac test 308 equipment 69 Schilling test 307-8 Ulcerative colitis 427 techniques 69 Voiding cystourethrogram 412 Ultrasonography Ventilation, regional47-8 Vomiting 299-300 Index 671

Von Recklinghausen's disease I27Xe ventilation lung imaging 518 282 comparison with ehest X-rays ventilation and perfusion 63 indices 71 Wallmotion 421 disposal problems 59 washout data 72 Warfarin 53 imaging characteristics 57, 59 washout technique 103, 188-9 Wash-in curve 71, 72 imaging technique 69 133Xe CBF study Wash-out curve 71, 72 rebreathing systems 69 with 245-detector system 178 Watershed infarction 176 regional ventilation studies blood-brain barrier scan 178-9 Wegener' s granuloma 177 68 helmet approach 178 Weis, Soma 1 restrictive lung disease 67 intra-arterial method 178 Whitaker's test 110 133Xe 17 measurement 188 White celllocalization study brain scanning 164 planar approach 179 605 cerebral blood flow (CBF) SPECT scan 179-80 Whole kidney transit time monitoring 162 133Xe clearance (WKTT) 94 comparison with ehest X-rays for blood flow measurement index 94, 113 63 87-8 Whole-body disposal problems 57 cystic fibrosis 66 camera system 88 imaging characteristics 57 regional ventilation studies 68 counters 551-2 imaging technique 69 sarcoidosis 67 imaging 547, 548 lung blood flow distribution 71 133mXe gas ventilation for neutron activation 388 lung ventilation radiotracing diaphragmatic lesions 340 scan in thyroid cancer 598 48-9 Xenon imaging technique 69 Wilson' s disease 336 rebreathing systems 69 Xeroderma pigmentosa 615 regional perfusion 70 Xerostomia 294, 295, 516 X-ray fluorescence for solitary regional ventilation cold nodule 215 measurement 70 90Y X-ray tomography for hone skin clearance rate 87 antibody labeHing 498 tumours 442 ulcer healing 87 generator system 517-8