IAEA-152
THYROID RADIONUCLIDE UPTAKE MEASUREMENTS
PAPERS PRESENTE PANEA T DA L MEETING ORGANIZEE TH Y DB INTERNATIONAL ATOMIC ENERGY AGENCY VIENNA, AUSTRIA ,197 Y 17-21MA 1
A TECHNICAL REPORT PUBLISHED BY THE INTERNATIONAL ATOMIC ENERGY AGENCY, VIENNA, 1973 The IAEA does not maintain stocks of reports in this series. However, microfiche copies of these reports can be obtained from INIS Microfiche Clearinghouse International Atomic Energy Agency Kärntner Rin1 g1 P.O. Box 590 A-1011 Vienna, Austria on prepayment of US $0.65 or against one lAEAmicrofiche service coupon. PLEAS AWARE EB E THAT MISSINE TH F GO L PAGEAL THIN SI S DOCUMENT WERE ORIGINALLY BLANK POREWORD
Tests of thyroid function based on measurements of the uptake of radioiodine by the gland (thyroid uptake tests) con- stituted one of the first diagnostic applications of radioactive tracers and have been widely used in the diagnosis and investiga- tio thyroif o n d diseases n I96 I Internationae . 0th l Atomic Energy Agency invited a group of consultants to draw up a standardized procedure for such uptake measurements. The recommendations of this group related primarily to measurements of the uptake of I 24 hours after its oral administration - the basis of the thyroid uptake test most commonly performe werd I96n i an de 0 - publishen i d a number of scientific journals.
Durin ensuine gth g decade thyroid uptake tests underwent con- siderable development. New radionuclides were utilized, new instru- ment d techniquean s measuremene th r fo s uptakf o t e were devisedd ,an n increasina g emphasi places swa uptakn o d e measurements made relatively soon after administration of the radioactive tracer. Parallel development took plac n testi e s f radioinvolvino e -us e gth nuclides but based on measurements of parameters other than uptake. In view of these advances the Agency decided in 1970 to convene a second panel of experts to review the status of thyroid uptake tests and to up-date, and where necessary amend, the I960 recommendations.
ThiAgency'e th s t panea t s lme Headquarter y Ma 1 2 so t fro 7 1 m s repor it 197bee s d ha t1nan submitte publicatior fo d scientifio t n c journal Englishe th n si , French, Russia d Spanisnan h languagese Th . various working papers presented durin meetinge gth , which contain information supplementary to that given in the report, have been gathered togethe thin ri s document orden ,i r thae tb they ma y available to all interested persons. CONTENTS
I CLINICAL ASPECTS Clinical requirements for thyroid radioisotope uptake measurement s ...... 1 . WAlexandeD . d J.Gan r . Shimrains Observation e rationalth n o s r thyroifo e d uptake measurement polemia : s c ...... 7 . C.C. Harri J.Kd an s . Goodrich
I I CHOIC RADIONUCLIDP O E E Radioiodine dosimetry and the use of radioiodines other than ^-^1 in thyroid diagnosis...... 13 H.N. Wellma d R.Tan n . Anger. Jr , Thyroid 1-131 uptake measurements and the determina- tion of effective half-life of 1-131 in patients with the rapeutic doses...... 31 H. Kakehi . Saegus. TatenK Y , d oan a
III EARLY UPTAKE MEASUREMENTS 99 m The measurement of thyroid uptake using To ...... 41 A. W.O. Goolden, H.I. Glas d E.Dan s . Williams 1 3 1 99m The measurement of the thyroid uptake of Tc , I and 2j a-t early times after isotope administration. 63 J.G. Shimmin W.Dd san . Alexander e measuremenTh kinetie th f o tc constant describing the thyroidal concentratio d organinan c "bindinf o g iodide and pertechnetate...... 75 J.G. Shimmins, J.¥.K. Robertson, W.D. Alexanded ran J . Lazarus Quantitative scintigraph e stud th earlf o yn i y y thyroid uptake ...... 1 9 . B. Bok
IV LATE UPTAKE MEASUREMENTS The performance of the IAEA standard collimator for thyroid radioiodine uptake measurements with fadio- nuclides other than 131i...... 121 R.G. Daou Spectral region assessment of the influence of thyroid dept thyroin o h d radioiodine uptake...... 5 13 . H.N. Wellman, J. Tieman and E.L. Saenger Method of measuring thyroid 1-131 uptake by a digitized scintigram of thyroid gland...... 149 H. . SaegusKakehK d an ia Thyroid 1-131 uptake measurement with a scintillation camera...... 157 H. Kakehi and K. Saegusa
SELECTED BIBLIOGRAPHY 165 CLINICAL REQUIREMENT THYROIR SFO D RADIOISOTOPE UPTAKE MEASUREMENTS
¥.D. Alexander and J.G. Shimmins University Department of Medicine Gardiner Institute; Western Regional Hospital Board Regional Departmen Clinicaf o t l Physic d Bio-Engineerinsan g Glasgow, Scotland
ABSTRACT
This paper discusses the clinical requirements for thyroid uptake tests in relation to other tests of thyroid function, with particular reference to the assessment of the response of the thyrotoxic patient to therapy. The 20-minute thyroid up- take test is especially useful for the latter purpose since t i indicate underlyine th s g functiona lthyroi e statth f s o ea d distinct fro s ratit m f hormono e e production usee r b fo dn ca , repeated assessment s i itsel d an sf unaffecte antithyroiy "b d d drugs.
Introduction
Thyroid function tests have been of great value in the diagnosis of
thyroid disease t untibu , l recently the/have bee managen i littlf no e eus -
ment. If in the thyrotoxic patient one wants to confirm the clinical
diagnosis, then thyroid functio ne othe th test n e usefulro ar shand , If .,
one want knoo t s w whether drug r destructivo s e treatment will ultimately giv bese eth t results, then thyroid function test usualle ar s y
of no help whatever. Help is needed because each form of treatment of thyrotoxicosis has a major disadvantage. As far as radioiodine therapy is concerned the chief trouble has been the high incidence of late hypothy- roidism. After subtotal thyroidectom incidence yth f relapseo hypod ean - thyroidism taken together has generally been considerable. The chief
I problem with antithyroid drug therapy is that half the patients relapse
after completin normaga l cours treatmentf eo coule on df I predic. t a t e beginningth r durino , firsmonthse w gth fe t treatmenf o , t which patients
would relapse and which would remain euthyroid after longterm antithy-
roid drug therapy, then treatment could be rationalized by using radio-
iodine or surgery for those patients unsuitable for drug therapy.
Diagnostie cUs
Chemical measurements (PBI, thyroxine iodine, free thyroxine
index) are used more frequently than thyroid radioiodine uptake measure-
ments. But considerable use of thyroid uptake measurements continues.
In one clinic the monthly figures were -
Thyroxine iodine estimations 500
Thyroid radioiodine uptake 50
Initial assessemen f Graveso t ' disease
We have reexamined the question whether any of the features of
thyrotoxicosis observed at the initial assessment correlate with a good
prognosis after antithyroid drug therapy. Factors "which sho wsignifia -
cant difference in the group of patients who remained euthyroid after
completion of treatment include goiter size, 2-minute thyroid radioiodine
uptake, 20-minute thyroid radioiodine uptake, and protein-bound iodine.
Assessment of response during antithyroid drug treatment
When assessing the response to treatment during antithyroid drug
therap requiree yon s informatio fouf no r different kings. 1. Is the patient hyper- eu- or hypothyroid, i.e., what is the level of
thyroid hormone production?
2. What is the underlying functional state of the thyroid as distinct
from the level of thyroid hormone production?
3. What is the prognosis, i.e., is the patient drug-responsive and
suitabl r longterefo m antithyroid dru grelapsee therapysh s i r -o ,
pron betted ean r treate operatioy db r radioiodineno ? f longterI . 4 m antithyroid drug therap s beinyi g given, when nca
treatment be discontinued?
The 20-minute thyroid uptake during antithyroid drug therapye Th .
ZO-minute thyroid radioiodine uptake measures a different parameter of
iodine metabolism compared with conventional uptake measurements
•whic s speciahha l clinical valu patientn ei s receiving antithyroid drug
therapy. This is because it reflects principally the iodide trapping
functioaccumulatioe thyroide th th , f e. o n . e i ,th iodidy f nb o n eio
thyroid gland. Radioiodine test thif o s s type allow assessmenf o t
thyroid function during treatment with antithyroid drugs, and are unique
than i t they indicat underlyine eth g functional thyroie statth f eo s da
distinct from the level of thyroid hormone production (Figs. 1 and 2).
The tracer dose has to be given intravenously since otherwise the rate
of absorptio t wouln gu fro e dm th interfer e 'wit resule teste hth th f .o t
Perhap s fai i dra o t t ri s analog n wa y betwee 20-minute nth e uptake
and the ESR during treatment of tuberculosis or rheumatic fever. The
ESR reflects the activity of the tuberculous disease and when it returns
normagoof o t o s di prognostit i l c significance. However, thero n s ei
guarantee that the ESR will not rise again, the result of reactivation of 3 diseasee t th seemi d an s, that exactl same yth e 20-minut s trueth i f eo e
thyroid uptake in thyrotoxicosis (Figs. 3 and 4).
Assessmen f Responso t e After Antithyroid Treatment
After antithyroid drug therapy is discontinued, it is usually unnecessary
to make measurements of both thyroid uptake and circulating hormone.
The latter alone is sufficient since the values are concordant. However,
in three patients unexpected results were observed.
20 Ml N. FREE T •IVROXINE UPTAKE0/ IN DEX Ml . .M •30 é"
20 Uptah«m M 0 2 %A •20
s HI Tniodothyrofiin» 10 -10 \\ —————— C'-*>\ . ^-^;a-»x««i^arr^t:^^TT^Î^=?=i-*'r-¥.hi.iTT:'r, ,-,-,-f, .. 777. ; ^ 0 4 6 3 2 3 8 2 4 2 0 2 16 8 '2
MONTHS
Fig. 1
Drug-responsive patient. Afte month8 r s treatment with carbimazole the 20-minute uptake fell below 1 %. Suppression of thyroid func- tion continue e nex monthth 2 4 tr fo ds until triiodothyronins wa e discontinued. Then normal values were observed. 20 MI N fR££ ÏHVROXINE UPTAKE'^ 'NDEX
MI ^ 80
A 70- •70
0 MUprak«u 2 t A % 60 60- • F.« Th,ro«in. Ind.« r Corbimaia!« v/-' ^ Triiodolhyronin. 50- •50
« 40- A
30 ^V * 20- \ V- 20 » \ \ K) V_. 1 \ _/— -""\X V' > ' ' 2 ' 1 '12 ' ' ' ' 1'a 'to ' ' 8 ' ' ' ' '20 4 ' ' ' ' '24 • ' 4 ' ' ' '282 ' '1 ' ' ' 'a ' ' 4 ' ' ' MONTHS Fig. 2
Relapse-prone patient. After 12 months treatment the thyroid uptake had not fallen. ¥hen carbimazole was discontinued there was an abrupt recurrence of severe thyrotoxicosis. A second course of carMmazole lasting 30 months was given.
20MIN. FREE TKYROXINE UPTAKE^ INDEX 40i * 40
M0 ni 2 . Uptok0 A % l / \ 1 0 3 30 11 / \ * ^ * Th/roxin* Index ra / \ Carbimoxol«
/ \ ^É Trtiodothyronine J 20
10 -^. /Kl 10 \ ^~v^<=^ S-V<\ 6 3 2 3 8 2 4 2 2 6 1 2 1 8 4 2 1 8 4 MONTHS
Fig. 3
Self-limiting recurrenc f thyrotoxicosiso e , after remaininn i g remission for one year following completion of antithyroid drug therapy. 20 MI N. FREE THYROXINE UPTAKE^ INDEX 40-) r40
10
S 12 12 16 20 24 28 32 36 40 46
MONTHS
Fig. 4
This patient remained euthyroid for approximately 3 years after completing antithyroid drug therapy d thee develope,an sh n d transient and incomplete features of thyrotoxicosis associated with elevated 20-minute thyroid uptake and free thyroxine index. OBSERVATION RATIONALE TH N SO THYROI R EFO D UPTAKE MEASUREMENTS: A POLEMIC
C.C. Harris and J.K. Goodrich Division of Nuclear Medicine Departmen Radiologf o t y Duke University Medical Center Durham, North Carolina, USA
ABSTRACT
This paper discusses the rationale for thyroid uptake tests e requirementanth d s that such tests should satisfys i t I . concluded that extremely precise measurements of uptake are not required and that relatively simple equipment and procedures usede b n A numbe.ca f requirementro s that shoul satisfiee "b d d are listed.
There have been many proposals directed at improvement of the thyroid radionuclide uptake measurement. These proposals chiefly have been concerned with improvemen e physicath f to l accurac measuremene th f o y t dealing with such factor s anatomicaa s l variation glann i s d sizd depthan e , extra-thyroidal neck activity, body background, etc. Some proposals, however, have been more con- cerned with reducing the amount of radioactivity involved and/or reducing the absorbed radiatio e patientn th dos o t e . Bot f theso h e objectives, singld an y in combination, are certainly worthy goals. Som f theso e e proposals involved method r equipmeno s t significantly beyon minimue th d m necessary complicatio r sophisticationo n . Indeed, some schema require multiple measurements with multiple detectors, clearly well beyon minimue th d m requiremen r estimatiofo t f "glano n d activity y comparab " - tive counting. It would seem appropriate in discussions leading to possible recommendations concerning standardized thyroid uptake measurement equipmen d methodologan t o t y examin e clinicath e l rational measuremene th f o e t itself. 7 Why are thyroid uptake measurements requested? What is their clinical value, fro mpragmatia c poin f viewo t ? Perhap usefua s l poine b f viey o t wma established by listing some of the reasons for thyroid uptake measurements and commenting on them.
Thyroid uptake e following usefue th ar sr fo l :
1. to provide evaluation of response to stimulation (thyroid
stimulating hormone, TSH suppressiod )an n (triiodothyroinine,
T-3 and thyroxine T-4) of thyroid function. Comment: Two measurements are required, one to establish a baseline
before stimulation or suppression and a second to
indicat e changth e e from baseline uptake.
o provid2t . factoa e r calculatiofo r f therapeutino c dosages
f radioiodineo rememberee b . o t Comment s i d t I tha: t
respons o radioiodint e e therapt necessarilno s i y y propor-
tional to uptake hence there are needed,
3. sequential measurement n suppori s f evaluatioo t f thyroino d
function after therapeutic dose e administeredar s . Comment:
The patient's symptoms may perhaps be better for evaluation,
hence the old saying, "Don't treat the uptake, treat the
patient's symptoms." However, trend f uptako s e measurements
might indicate response to therapy more quickly than would
be possible without them, though T-3 or T-4 studies might be as
effective.
4. to provide a means of study of organification in the presence
of enzyme defects in familial goitrous cretinism. totaa para f s o a tl . endocrin5 e evaluation.
othee b Ther y r ma epurpose s claimed t thesbu , e constitut majoritea y
of clinical applications. f theso l eal situationsn I , comparison countin patiene th f o g t againsa t reasonably chosen"standard," carrie t witdou h good technique s probabli , y quite
sufficien r adequatfo t e clinical results certaia o T . n extent e patienth , t
"controln e baselinow th s serve n hi i " s ea s study, thus providing some relief
from the need for physical assay of gland activity of extreme or absolute
accuracy. The only "accuracy" required is that needed for establishment of
ranges of normal and abnormal response.
In further assessment of the value of the thyroid uptake, it is to be
noted that it is of limited value when used alone. Rather, the thyroid
uptake measurement is generally used as a part of a thyroid screening profile
(1). A single thyroid uptake measurement, unaccompanied by other function
studies, does not indicate:
1. distribution of activity within the gland
2. functioning extra-thyroidal tissue
3. positio thyroie pituitary-thyroie th th f no n di d
axis (degree of autonomy). A hyperfunctioning
autonomous nodul accouny ostensibln a ema r fo t y
euthyroid uptake and, indeedsuppressine b y ma , g the remainde glande th f o .r
4. iodine-starved gland. Thi s importani s n iodinei t -
poor regione worlth f do s wher hypothyroia e d person
may present a "hyper-trapping" thyroid gland.
5. chronically high levels of exogenous iodine, present
in the diet and medications in affluent countries.
Therefore, a single, isolated, thyroid uptake measurement, for which there shoul some b d e clai f mneeo r extremfo d e physical accuracy f limiteo s i , d clinical
value and may even be misleading. In view of these clinical considerations, it is our position that the thyroid uptake measurement does not merit the use of highly complicated methods nor intricate devices in an effort to obtain an extremely precise assay of thyroid radioactivity believe H . e clinica th tha n i t l rational e thyroith f o e d uptake measurement ther s i nothine o indicatt g e nee r anythinth e fo d g other than careful technique using properly operating simple equipment. Our concept of "simple" equipment includes a scintillation counting system consisting of: l (TlNa ) n scintillatioa . 1 n crysta 5 cms 2. 5 cms .2. x l. r largero , 2. some sort of means (collimator) for confining the field of vie f thawo t detecto o about r t 15-20 cmsn diametei . r at 20 cms. crystal-to-skin distance. 3. at least threshold discrimination as a means of energy- selective counting ("window r spectrometrio " c counting is cerainly desirable, though by no means essential). In addition we believe that this simple equipment should include: a spectrall . 4 y competent neck phanto r holdinmfo e th g "standard" source. 5. an attenuator to eclipse, but not completely obliterate, activity in the thyroid gland. (Me do not agree with e statementh f pagn Measuremeno o t 8 e f Radioactivito t n I y Body Organs, Reporn IAEa Af o tPanel , which states i t "I s important that the shield be thick enough to ensure that no radiation originatin e thyroith n i g d itsel s recordei f d during the background measurement.") A certain penetration by radiation of the Oak Ridge B filter (2) was a part of e rationalth e "ORINth f o eS methods".
10 6. means of positioning the principals in the measurement with respect to each other such that reproducibility is easily obtained. 7. a procedure that is simple, requiring the absolute minimum numbe measurementf o r s without movemen e detectorth f o t . A"B-filter" extra-thyroe b t no y backgrounl ima da r o y ma d spectrally or physically superior to a "thigh background." However, it requires no movement of the detector with respect to the patient, and may thus reduce technical error. e simplesth e submiW f o te tequipmenus thae th t d methodologan t y possible in thyroid uptake measurement s consisteni s t both wite clinicath h l rationale of the measurement and the means easily available throughout the world.
REFERENCES
(1) BRUCER, M., Thyroid Profiles: The Decline (but not the Pall) of Uptake, Vignettes in Nuclear Medicine, No. 40> Mallinckrodt Chemical Works . Louis,St ,
) BRUCERCalibratioe (2 Th , ,M. n (and Salvation Thyroif )o d Uptake, Vignettes in Nuclear Medicine, No. 39» Mallinckrodt Chemical Works, St. Louis.
) BRUCER(3 Thyroi, ,M. d radioiodine uptake measurements A standar. d system for universal intercomparison. USAEC Rep. ORINS-19 (1959).
11 BADIOÏODIN RADIOTODINEP O EE DOSIMETRUS E TH SD YAN OTHER THAW 131 ITHYROIN I D DIAGNOSIS
ÏÏ.N. Wellman and R.T. Anger, Jr. Nuclear Medicine Laboratory 5 Radioisotope Laboratory University of Cincinnati Medical Center, Ohio, USA
ABSTRACT
Of the 24 radioisotopes of iodine, only four, I, I, "I and 132I have been utilized clinically to any significant extent. Optimal use of radioiodine involves the consideration of a particular isotope's physical properties in relation to the economics and logistics of shipment, the quality of generated clirical studies, and radiation dosimetry.
"t O "3 1 9 R "I "Î O In this paper, I, I and I are critically evaluated with reference to each of these considerations. In terms of absorbed dose 123 132 to the thyroid, " I and I are the isotopes of choice, giving doses abou respectivelyI t 1/7 dose 1/10d d 0th an an e f I fro0o .m 132 Becausabundans it f eo t high energy photonsimpracticas i I , r fo l thyroid imaging procedures. Its very short half-life and availability igeneratoa n r system, however, give advantage w radiatiolo f so n dose and applicabilit n seriai y l thyroid function studies e relativelTh . y -I pC long half-life (60 days) and ready availability of I are economical advantages. Equivocal clinical results and an only slightly lower radiation dose however , I than e significan,ar t disadvantagese Th . 123 isotope I, in addition to giving a low radiation dose, theoretically provides the best combination of physical properties for clinical 123 utilization. Until now, however economice productio,I th f so d nan contamination with the higher energy isotope, I, have limited its utilization. contaminationI Despit e eth , high resolution images have been obtained, particularly wit hgamma a oamer pinhold aan e collimator, and newer methods of production hold promisé of large amounts 123 of high purit. I y
Clinical use of radioiodine isotopes Thoug hpossibl4 2 ther e ear e radioisotope iodinef so , only eight have potential use in medicine, namely those with mass numbers of 121, 123, 125, 1?8 126, 128 132,d 130an .1 ,Cyclotro13 n produce witI hd onl 25-ninutya e half-lif firse th ts ewa radioiodin ealmosn usema n i dt simultaneously y"b 13 Hertz, Roberts and Evans (l) on the East Coast and Hamilton (2) on the West -i oQ Coast. After this initial attention, little other use of I has been s nevereportedha t ri received ,an d active clinical use. The four radioisotopes of iodine that have reveived the most clinical 123 125 131 132 wit, I h theid an rI principl , attention^1 e properties, I , e ,ar noted in Table I. A number of factors are important in the choice of a. radioisotope with optimal characteristics. These factors mus consideree b t d in light of the particular circumstances extant in a particular clinical laboratory .e importan th Man f o y t properties involve optimizinn i d e us e th g of radioiodine are detailed in Table I. These factors narrow down to three general considerations, namely, the economics and logistics of shipment, quality of the clinical studies and the radiation dosimetry.
Those radioisotopes with shorter half-live acceleratod san r production mose th t e expensivar d difficulan e obtaino t e qualitclinicae Th th . f o y l procedures is very dependent on the characteristic gamma radiations and their abundance. Photons of either very low or very high energy can interfere with optimizatio f studieso n energiew Lo . s resul considerabln i t e tissue absorp- tion whereas high energies resul appreciabln i t e collimator penetration. Dosimetry, to be covered in detail in the later portion of this paper, is dependent on the mode of decay and the physical half-life.
For diagnostic purposes, it is preferable that a radionuclide have only penetrating radiation practicen I . half-life ,th eo longe n nee e b dr thae th n biological event being measured. Wagner and Emmons proposed the average life as a practical measure of the optimization of the physical half-life (3). closee th averag e Tha, rth tis e life approximate biologicaa e tim f sth o e l event more th , e dosimetrys ideait s i l . However, particular clinical circum- stances must dictat optimizatioe th e radioisotopa f no f iodinee o eon n I . circumstance, economics may dictate the use of a radioisotope that results in bot highea h r radiation dosd lesan es tha optiman na l quality clinical study. Ideally ,a radioisotop iodinf o e clinicar fo e e shoullus readile db y available d economicalan , should hav optiman a e l abundanc purf o e e gamma photon r higsfo h resolution collimation and minimal tissue absorption, and should have an average life approaching the time of the biological event, with the least radiation dose possible. Each clinician will thusn havow mako s t e ehi optimization between these extremes. e otheon Limitef ro radioiodin e us d e bees isotopeha n , I reporte, d an d is briefly mentioned. Its favourable 12.5 hour half-life is somewhat outweighed 14 by the high energy 1150 and 740 keV gamma photons for routine clinical use. e studth f Pfannenstie tota) o yn havi (4 e el . us bodreporteal t s yit ej l n o d retention of radioiodine after thyroid stimulating hormone (TSH) in post- surgical thyroid carcinoma patients.
Iodine-132 This radioiodine isotope has received most clinical use in Europe, particularly in England. It is the shortest lived radioiodine in clinical use, consequently wit shora h t average availabl s i life t I . e frodecae th mf 3.2 o y - day fission-produce generatora n i e T ,d offsettin132 shors git t half-liff o e 2.3 hours (Table l). Azeuedo and Trancoso (5) have reported generators to be useful for up to 3 weeks in remote laboratories. As will be seen in dosimetry calculations, the ß~ particles emitted during the decay are offset by the short half-life, resultinradiatiow lo a n gi n dosunir pe et activity. Consequently, 1 3? some investigators in Europe have used I only in children (6). Of primary concern, however, are the very high energy (Table l) gamma photons which make collimation difficult impossiblet no f ,i . Becausshore th tf o ephysica l half-life, thyroid measurements mus made tb e soon afteinjectionI r 132 , usuall hours4 t ya , when body backgroun stils i d l very high from the residual high concentration in the inorganic iodide space. The high-energy gammas would appear to make body background correction subject to considerable measurement errors. LevAshburd an y ) hav(7 ne reportea n o d technique that apparentl s relativha y e clinical value. However, they indicate that the prime use of 132I is for study of variations in the same individual with time and pharmacological manipulation, and they do not recommend the test in the general patient population due to the low differential uptake range between extreme thyroif o s d function (8). Twenty-four hour radioiodine uptake seeo t m have a wider acceptance and the 3.3-hour average life does not approximate the timing of this procedure.
As Levy and Ashburn have reported, a prime asset of 132I is the study of thyroid function with special uses such as pharmacologie manipulation with tri- iodothyronine (T, TSH,becausd )an e repeatee testb n sca closn i d e temporal relation- 11), 10 shi., Wit(9 p h longer-lived radioiodines, contributions from previously administered activity introduce significant errors in subsequent measurements. Practical thyroid imagin bees ha g n impossible witI b sai o ht d 132y eb 132 Myer excludeo swh fro1 liss clinicallJ f hi smo t y useful radioisotope iodinf so e (12). Collimators for use with 1 \*2I could be designed, but would affect the 15 132 radiation dose advantageplu, I s imagin r fo s g woul de don b hav eo t ewit h unacceptably high body "backgrounds. Nonetheless, Guntermann has reported success- T 'JO ful scintigraphy with I (13). It is doubtful if the procedures described would 132 be widely adopted. Thus I does have advantage in low radiation dose, serial thyroid function studies, but probably does not have place ir the general nuclear medicine laboratory because of its poor imaging properties.
Iodine-123
e longesth f Iodine-12o te physicaon s 5ha l half-livese th days0 6 t , ye , lowest-energy photons of any of the clinically used radioiodines (Table l). These characteristics make possible certain unique capabilities in diagnostic studies with this radioisdope s Myer a ,s outline ha s d (12). This radioisotop s readila s i e y available as I in most areas, and indeed its long physical half-life gives it some additional economic advantages. Estimates of its radiation dose vary widely 1 9 A e anprobabldar y dependent upomisconceptioe th n photonI penetratins f sa o n g radiation, as wil] be discussed under the dosimetry section. In terms of 24-hour thyroid uptake determination, I has an exceptionally long average life. The 125 quality of clinical procedures with ''I is very dependent upon a number of technical factors, which, if not recognized, can certainly deteriorate or even nullify results. Great care must be taken to assure thaf one uses properly designed instrumenta- 125 tion with I. With a half value of only 0.17 cm in aluminium, one must be certain to use Nal(Tl) crystals "canned" with the thinnest aluminium foil. Also, satisfac- tory electronics must "be utilized. Presently gamma cameras cannot be satisfactorily employed with such low-energy photons. Of critical importance to the use of this radioisotop e significanth s i e t tissue absorption half-valuem c 8 1. o ,t -i.e7 1. . layer (Table l) . Iodine-125 used for thyroid function studies must employ appro- priate measure r thyroifo s d depth correction. Studier laboratorou n i s r fo y correction of thyroid depth have indicated an average thyroid depth of 2.6 cm with o (Fig.l)c 5 4« o .t Riccabon6 a rang0. f o e a (14 alludes )ha thio t d s problem: however, the only accurate approach to thyroid depth appears to be that advocated y Rollb o (15)« This technique employ inverse th s e square principle with thyroid countin . Howevercm 5 2 g distanced , an wit tissue 8 1 hth f so e absorption factors offsetting the high photon abundance, the standard measuring distances plus the more recent higher radiation dose estimates from C "O l I (see dosimetry) would not seem to give the radioisotope as much clinical advantage as proposed by Rollo (15). Photopeak to Compton-scatter correction as published by our laboratories (16) is not feasible with 125•'I because of the extremely low photon energy.
16 e Tissue absorption factor alse sar o significan thyroin i t d imaging. I with 12 ) More superficial aspects of the thyroid are going to be imaged with greater efficiency. Substernal thyroid extension may be a particularly difficult problem TOC IOC, with I. Clinical studies with 5I by Riccabona et_ aJU (14) to intermediate by Charkes et al. (17) to no advantage by Artagaveytia et al. (18). Moll ej al. 125 have reported thaI scintigrapht t tissua y e depths greatee rar a thaer 2 n inferior to 131I or 99Tcm. (19).
There has been some agreement that 125^1 can be useful in delineating superficial thyroid nodules (20), which may be its principal imaging advantage.
n "5 O T O f\ In contrast to I, use of I for pharmacologie manipulations such as with T.. and TSÏÏ would appear to have the same drawbacks as I, namely continued retention by the thyroid gland. On the other hand, for evaluation of long-term biological events such as radioiodine kinetics, the long physical half-life of 125 I can be used to advantage, especially in children, as we have previously reported (2l). Although not in the scope of this paper, it must be emphasized that 125 s distincha I t advantage n varioui s n vitri s o studie f thyroio s d function (12).
Iodine-123 123 Myers has stated that " I fulfills the criteria for an ideal gamtr.a isotope more than any other radioisotope of iodine" (12) and, theoretically, this appears to be true. He has reported initial early work with low resolution scintigraphy 13.3-houe (22)Th . r half-lif s certainli e y long enoug o accomplist h h satisfactory clinical studies, indee e averagth d e lif f 19.o e 2 hours approache e 24-houth s r thyroid uptake time more closely than any of the other radioiodine isotopes (Table I). The 159 keV gamma makes collimation nearly ideal and has a very satisfactory tissue half value layer of 4-7 cm. Pure electron capture decay plue relativelth s y short half-life e lowesresulth n i tt radiation absorbed dose s discussea , , I saved later. purposesl al r appearI Fo , s ideal: however12 3morf o , e concern than e otheth f ro radioisotopewit y han f iodinemodee so th productio f o e s ,ar d nan the concomitant economics. This radioisotope can be produced only in an accelerator numbea y b f reactions ro t ,bu continuet I . commercialle b o t s y 12 ^ availabl Bidgk eOa froe th Nationam l Laboratories e (p,NT , produce )e th y db I reaction, and is very expensive compared with I or I. Our initia exploratioe laimes th enthusiaswa t da I f no r mfo 123 alternate, less expensive, production techniques for this radioisotope. Sodd «it al. (23) have recently reported our results to date with most of the possible 17 production reactions. As a consequence of the extensive studies, we have advo- cated the indirect production technique of 122Te(4H,3n) I2\e 2>1 hl> I2^I for reasons explained "below ultimate Th . e economic r commerciafo s f thio e s us l reaction are the subject of continuing investigation.
Our early, initial clinical studie thyroi0 3 n i s d patients were designe comparo t d I witI assumineh e theoreticagth l advantagee th f o s more ideal radioisotope (24) high-resolutionA . , low-energy 1045-hole collimator (Fig. 2) was used for I and a 31-hole, medium energy collimator for I. 123 In addition I imagin don,s ewa g wite gammth h a camer pinhold an a e collimato. r Both 28 and 159 keV images at 6 and 24 hours were performed with TOT I at approximately equal information densities e resultanTh . t studies were reay db a blinded technique by a panel of four physicians. To our disappointment, I images were still preferred, with gamma camera images being preferred . I with Twenty-eight keV studies were judged inferior.
Further analysis of cyclotron products including our own as well as those of ORNL revealed higher than anticipated amounts of I, as reported by Sodd _e_t al . (25). Goolden e_t a_l. (26) have also reported on the problem of 3 12 4 12 contaminatioI clinican i n studiesI l .
Additional studies were performe evaluato t d I effece th e f o t contamination on a thyroid scanning system (Fig. 3). Thirty-one-; 73~and 1045" hole collimators were evaluatede seenb high-energe n ,th ca s A . y (511» 602, 722 and 1690 keV of l) scatter contribution to the 159 keV photopeaks of 1 O 1 approximatels i I ) wity31-hole 3$ equath h , (2 le collimator with purr o e 3 12 3 12 contaminate . HoweverI d , high energy scatter with contaminate repreI d - sents 28 18 photos were considered, overall, to be superior to the rectilinear scans. The dose reduction resulting from the use of 123I should "be stressed, especially as regards studie children i s pregnand nan t women. More recently, a limited number of patients have been studied with commercially availabl . StudieI e s containin witI levea t hf a o l I g shoc abouf w0 1 tdegradatio f resolutiono n whe e 73-holnth e collimatos rwa utilized. Very good views were obtained with the 31-hole collimator and the "O 1y l gamma camera. Similar studies at a level of I contamination of 29 i° produced image inferiof o s r quality wit73-ane th h d 31-hole collimators. However, excellent images were obtained wite gammth h a camera must I .e emphasizet b d that despite I contamination, in all our studies, gamma camera images were of as high a quality or superior to rectilinear scans. We have postulated that these superior results hav two-fola e d explanation. Firs allf o t tungstee ,th n inser d singltan e pinhole combination witgamme th h a camera eliminate th e scattering of the high energy photons (511, 602, 722 and 1690 keV) of I from the septa in the focusing collimator used with rectilinear scanners. Secondly 0.5e Na 19 In summary, clinical utilizatio theoreticae th f no l ideal character- bees ha nI somewhaistic f o s t hampere presence high-energe th th y b df o e y pinhole th e interim f th contaminanto e r e collimatoFo ,us e gamm. I th ad , ran scintillation camera see o obviatt m e resolutioth e n problem n imagini s g with contaminated 123I, resulting in high quality images. Further development of 123 indirect methods of production of high purity I, especially if made more 123 economical, will greatly increase the potential use of I. Lastly, promise of 123 production of multicurie amounts of I has been suggested through the use of high energy photon accelerators and spallation reactions (Fig.5). It is antici- pated that contamination s greata wil greatea e lb r ,o r problem, with direct 123I production by these techniques. We anticipate that the indirect reaction througultimate th e wilX e e founb lb h o et d12 economicae answe3th o t r l spalla- 123 tion production of large amounts of I of high purity. Radioiodine dosimetry e averagTh e absorbed e totadoseth o specifio lt t s bodd an y c organs 123 12'5 131 132 from I, I, I and I are presented in Table II. These values were calculated according to the schema of Loevinger and Berman (27). ^» f 3 ju Sfjn t « ^j ~ m •*• -1 •L e averagth Whers i e D e cumulativ dos th n rads i es i ,À e activit (jCi-hn i y , targee equilibriue th mase th n gramsf th i s to s i s i m A , m dose constann i t absorbeg-rad/|^Ci-he th s i d0 fractiond ,an . The nuclear parameter sfoue (A.th r r radioiodine)fo s were taken frowore f Dillmath mo k n (28, 29) purposer .Fo f doso s e computation, these equilibrium dose constants were divided into penetrating and non-penetratir.g as absorbe e showTh Tabln i n. d II e functioa fraction s a ) photof . o n (0 s n 3. energy are available in MIRD Pamphlet No. 5 (30). However, for the absorbed doses present in this paper, an effective absorbed fraction (^) for all the penetrating radiations from each radioisotope was utilized. The same Mnnte Carlo approach described in MIRD Pamphlet No. 5 was employed, but absorbed fractions were obtainecomplete th r fo de photon spectrum rather thar nfo individual photon energies. When multiplie e totath ly b dpenetratin g equili- brium dose constant (J5 £ A. ) , the value obtained is equivalent to the computa- tio f ÎLAo n .usin. $ individuae gth . value0 l MIRn si DA Pamphle . 5 . tNo summary of these effective absorbed fractions for the radioisotopes of iodine is presented elsewhere (31). 20 00 The cumulative activities, A, were determined as JA(t)dt. The biological distribution functions used were approximations of computer solutions derived fro. iodinBermae al th m t e n model (32 d represen)an average th t e normally functioning adult thyroid. The maximum thyroid uptake of radioiodine was assumed to be 27 $, and the final thyroid biological half-life was taken as 8 days6 . Bot f theso h e assumption e base sar human o d n data reviewe a recen n i d t publication by Wellman e_t _al_. (21). It is readily apparent from the dosimetry data given in Table II that, s expecteda absorbee th , casel al e e thyroilimitind n th sth dosi o s t ei d g factor-, Wite exceptio, thesth h'I e absorbef o n d dose e slightlsar 125 y lower thae th n previously published estimates summarized by Hine and Johnston (33). This is presumably attributable in part to more precise biological and physical parameters utilizatioe th d absorbee an th f o n d fraction metho f dosiraetryo d t shoulI . e b d noted that specific absorbed fraction (-^-) were used for the thyroid dose calcula- tions. Based on extensive autopsy data, Wellman et al. (2l) found an average adult thyroid weight of 16 grams, but the currently accepted standard for thyroid weigh approximatels i t 0 gram2 y s availabl e (34)th d »an e absorbed fraction data (30, 31) have been calculated using this latter figure. Previously published estimate e absorbeth f o s e dthyroi th dos o t ed from -^1 range from 0.4 "to 1.4 rads/|j.Ci (33). The estimate given in Table II suggests thahighee th t r value e morsar e realistic e loweTh . r estimatey ma s possibl e attributablb y n overestimatioa o t e penetratine th f o n g characteristics of the radiations from 125^1 . The penetrating radiations from 125 I account for 33 i° of the absorbed dose while representing 66 $ of the available energy. On the -i o "5 other hand, the penetrating radiations from I account for only 27 $ of the absorbed dose while representing 86 $ of the available energy (see Table III). This same reasoning can be used to indicate the significance of the ß penetratine Th . radiationI g d radiationan sI emittedecae th f so yn i d absorbee th f 3 °o 1 respectivelyI daccound dose an d onlr $ an fo ts8 y I fro,m while representing 61 $ and 82 $ respectively of the available energy (see Table III). 2 13 123 Based strictly on dosimetric considerations, either I or I would e radioiodinbth e e isotop choicf o eclinicar fo e l procedures, sinc e thyroith e d R "9 I absorbed doses from thes isotopeo tw e e abousar t dose d 1/7th an e f I 0o fro m about 1/100 of the dose from I. This is of particular importance with respect to radioiodine studies in pregnant women and in children (2l). 21 Inherent in the thyroid absorbed dose computations presented in this paper is the assumption that the radioiodine is uniformly distributed within the thyroid gland. Ultimately, thyroid dosimetry must consider the actual distribu- tion of the radioiodine at the cellular level, since radioiodine concentrates in the thyroid follicles (35). Such a non-homogeneous distribution of activity represents more of a hazard than homogeneouä distribution due to the potential existenc verf o e y high absorbed dosea smal n si l amoun f tissueo t . Anspaugh (35) s considereha non-homogeneoue th d se thyroi th distributio conn d i dan -I f o n cludes that the absorbed dose remains essentially homogeneously distributed. othee Simila th valie b rr t radioiodinfo drno assumption y ma r o ey isotopesma s with their different spectral compositions energw ,lo s particularlyit d an I y 125 radiations, as suggested by Myers (12). REFERENCES ) HEETZ(1 ROBERTS, ,3. EVANS, ,A. , R.D. Proc. Soc. exp. Biol. (N.Y.) JJ8 (1968) 510. ) HAMILTON(2 . Amer,J Physiol. .J 4 (1938.12 ) 667. (3) WAGNER, H.N., Jr., EMMONS, H. In "Radioactive Pharmaceuticals", AEC Symposium Series No. 6 (CONF-651111), USAEC, Division of Technical Information (1966) p.l. (4) PFANNENSTIEL, P., SITTERSON, B.W., ANDREWS, O.A. J. nucl. Med. (19689 . )90 ) AZEUEDO(5 TRANCOSO, ,M. . ,IntW appl. .J . Radiât. _16 (1965L )4 (6) VALLEE, G., LUMBROSO, P. Sem. Hop. Paris 40 (1964) 926. (7) LEVY, B.S., ASHBURN, W. J. nucl. Med. 1_0 (19^9) 286. (8) SOUMAR, J., ROHLING, S., REISENAUER, R., VOHNOUT, S. Cas. Lek. Ces. 104 (1965) 1206. (9) BAYLISS, R.I.S. Proc. roy. Soc. Med. _6_0 (1967) 303. (10) PO¥ELL BLIZZARD, ,G. clin. J . ,R Endocr. _2_6 (1966) 1389. (11) BLEHA, 0., SCHULLEROVA, M. Sborn. Led. _6_9 (1967) 226. (12) MYERSn "RadioactivI . ,W e Pharmaceuticals" SymposiuC ,AE m Series 6 (CONF-651111) . No , USAEC, Divisio Technicaf o n l Information (1966) p.217. (13) GUNTERMANN MITTERLECHNER, S. , . .E Radiol . Diagn (1966_ .] ) 347. (14) RICCABONA Engw Ne .Med. J (1965. 3 ,G 27 . ) 126. (15) ROLLO, F. J. nucl. Med. 1_2 (197l) 8. (16) WELLMAN, H.N., KEREIAKES, J.G., YEAGER, T.B., KARCHES, G.J., SAENGER, E.L. J. nucl. Med. 8. (1967) 86. (17) CHARKES, N.D., SKLAROFF, D.M. Amer Roentgenol. .J (19630 .9 ) 1052. (18) ARTAGAVEYTIA, D., DEGROSSI, 0., GOTTA, H., PECOEINI, V. Rev. clin, esp. j?8 (1965) 266. 22 (19) MOLL , SINAGOWITZE. , , BORNERE. , , EATJE W. . , E Nucl, . -Med. (Stuttg.) l (1968) 8. (20) ROSSi; H., FERRI, P., TREVANO, G.Q. Minerva Chir. 20 (1965) 499. (21) WELLMAI, H., KEREIAKES, J . , BRANSON, B. In "Medical Radionuclides: Radiation Dose and Effects", AEC Symposium Séries No. 20 (CONF-691212), USAEC, Divisio f Technicao n l Information (1970 . 133p ) . (22) MYERS . J ,nucl W. .G . Med (1966_ .1 ) 390. (23) SODD, V.J., SCHOLZ, K.L., BLUE, J., WELLMAN, H. N. Cyclotron production of 123 evaluation a i- nucleae th f o n r reactions which produce this isotope, USPHS Rep. BRH/DMRE 70-4 (19?0). (24) WELLMAN, H.N., SODD, V.J., MACK, J.F. In "Frontiers in Nuclear Medicine", (HORST, W., Ed.) Springer-Verlag, Berlin (l 97 l). (25) SODD, V.J., BLUE , J. SCHOLZ,n "ThI . eK , Use f Cyclotrono s n i s Chemistry, Metallurgy and Biology", Proceedings of a Conference held at St. Catherine's College, Oxford, September 22-23, 1969, (AMPHLETT, C.B., Ed.) Butterworths, London (197 1) p.125« (26) GOOLDEN, A.W;G., GLASS, H.I., SILVESTER, D.J. Brit . J Radiol. . _41 (1968) 20. (27) LOEVINGER , BERMAF R. schemA , . r absorbed-dosM fo a, e calculations for biologically-distributed radionuclides, Medical Internal Radiation Dose Committee Pamphlet 1, J. nucl. Med., Suppl. 1 (1968). (28) DILLMAN, L.T.Radionuclide decay scheme d nucleaan s r parametere us r fo s in radiation-dose estimation, Medical Internal Radiation Dose Comir.ittee Pamphlet 4, J. nucl. Med., Suppl. 2 (1969). (29) DILLMAN, L.T. Radionuclide decay schemes and nuclear parameters for use in radiation-dose estimation, Part 2, Medical Internal Radiation Dose Committee Pamphlet 6,,J. nucl. Med., Suppl 4 (1970). . (30) SNYDER, W., FORD, M., WARNER, 0., FISHER, H., Jr. Estimates of absorbed fractions for monoenergetic photon sources uniformly distributed in various organs of a heterogeneous phantom, Medical Internal Radiation Dose Committee Pamphlet 5» J« nucl. Med., Suppl , (1969)3 . . (31) WELLMAN, H., ANGER, R., Jr.. ROHRER, R. Radiation dose to humans from 12 123i, 124l, 5j, 1^6If 130l, 13li ana 132Z administered as iodide ion, Medical Internal Radiation Dose Committee Pamphlet (in preparation). (32) BERMAN , . HOFF M , , BARANDESE. , , BECKERM. , , SONENBERGD. , , BBNUAM. , . R , KOUTRAS . J clin . D ., Endocr. _2_8 (1970) 468. (33) FINE, G.J., JOÏÏF3TON, P.T? , J rucl. . Med l .] (1970) 468. (34) INTERNATIONAL COMMISSIO RADIOLOGICAN O N L PROTECTION "Radiation Protection. Report of Committee II on Permissible Dose for Internal Radiation". ICRP Publication 2 (1959) 151. (35) ANSPATJGH . L Specia, l problem f thyroio s d dosimetry. Consideratiof o n 131j a functiodos s a e f groso n s sizinhomogeneoud an e s distribution^ USAEC Rep. YCRL-12492 (1965). 23 ce o 1 — 1 I- > ce LU «^ o O ce •z. •z. •z. \- ce LU o o o < ra _ i 1 — 1 1—4 •-e c • o LU CO CO CO LU 00 CJ CO CO CO Z o t—, t-t in ^ LU. u_ LL CD X-N CO O CO 00 CNI LU LU UD Q_ 00 hO IO CD 0* H i— O O D Ö CD LU 00 o CO CD r-H CNI CO CO LU oo oo r^ o o (=> n: CD O- LU LU X-N x^ en i—i _I LU LU •=r x-s CD ^ ^^ OQ _H l t- ÜD C O O O ^ Oh O < z X_" -3 x O (_ v^> x -v_ U LU Q- CO < en LO -ct~ f^x LU OO -- Z Q tn hn to I-H O. O O Z CO z i— r> LU O C N O —X— D C X S X— > ce < c c: e X-N hv. X-N CD CD o_ D_ CNI r>o en I~H r*o ce ^ ^- ^s ^- i ei— n o ^^ -^ CD CD CD oo oo cr i^» CNI O L O t O t I CNCN I >• co < LU O Q LU O LU LU LU UJ a Q m < LU ce LL. CNI LU IM i i— o crt > H i- O t—O l : n Q Q r CNI r\ C3 r—\ t*\ - UD - - I CN o o n CO CO |V>l LO CNI CNI CNI 24 TABLE II AVERAGE ABSORBED DOSES* ORGAN MASS RADIOIODINE ABSORBED DOSE (GRAMS) MASS NUMBER (RADs/jjCi ADMINISTERED) 6 THYROI1 D 123 ,015 125 1,04 131 1,5 132 ,015 LIVER 1833 123 , 00003 125 ,0005 131 ,0005 132 ,0001 STOMACH*0 16 * 123 ,0009 125 ,001 131 ,008 132 ,006 SALIVARY 80 123 ,0007 GLANDS 125 ,004 131 ,007 132 ,006 OVARIES 8,8 123 ,00001 125 ,00001 131 ,00005 132 ,00001 TESTES 38 123 ,00002 125 ,00001 131 ,00004 132 ,00004 RED 1500 123 ,00002 MARROW 125 ,0002 131 ,0002 132 ,00004 TOTAL 70000 123 ,00003 BODY 125 ,0006 131 ,0008 132 ,0001 *THE UNCERTAINTIE THESN I S S HIGA E S 50%A E VALUEHB ,Y MA S **FOR PURPOSE F DOSIMETRYO S E UPPETH , I CONTENTG R S HAVE BEEN ADDED TO THE STOMACH CONTENTS DUE TO THEIR CLOSE PROXIMITY, 25 TABLE III TOTAL EQUILIBRIUM DOSE CONSTANTS (G-RAD/JJCI-H) RADIOIODINE PENETRATING NONPENETRATING MASS NUMBER 123 ,3671 ,0591 125 ,0878 ,0446 131 ,8042 ,4134 132 4,9035 ,9982 26 DISTRIBUTIO F EFFECTIVNO E THYROID 20 n 15- Effective thyroid depth = distance from surface of neck to center of activit f eaco y h thyroid lobe o U_ 10- I I- 6 0. 9 0. 2 1. 5 1. 8 1. 1 2. 6 2. O 3 5 3. 0 4. 5 4. Effective dept . f thyroio hcm n i d Fig. 1. Effective thyroid depth distribution -in a grou patientf po s studies wit photoe th h - peak : Compton ratio method of uptake. 27 1045 31 hole collimalor hole collimotor Or OB |Z6 16 24 32 38 ) 1 42 40 46 (8 in 5.0 56 , I I I I.I I I M , 04 in 0.5 05 in Distance from oxis Fig. 2. Isoresponse characteristics of a 1045 hole high resolution low energy and a 3-1 hole medium resolution high energy collimator 99m 0 16 18UkeV20 0 0 14 16 180keV200 0 0 0 12 14 16 180keV200 0 0 12 14 120 —— mCe. • '"1. — —'"I I (5V"' . . contominotion) Fig. 3. Effect of high energy photon scattering on 1045» 73 and 31 hole collimator systems on photopeaV ke 9 th 15 e1f 23l ko . 28 I2H 10- IO O X s û_ o 5- 3.8 cm 0 0.8 0.7 0.6 Fig . 4 .Photopea o scattet k r standard corrections curve a famil r f fo sthyroio y d phantoms with "mock 123l» - 139Ce. 29 SPALLATION PRODUCTION 123F *O I 127I (P,5N) 123XE P* > 123I 126TE (P,4N) 123I *IN SYNCHROCYCLOTRON OR LINEAR ACCELERATOR PROTONV ME 0 S20 . Fig5 Spallatio. n reaction r direcfo sd an t indirect production of ^^1. 30 THYROID 1-131 UPTAKE MEASUREMENT AND THE DETERMINATION OP EFFECTIVE HALF-LIFE OF 1-131 IN PATIENTS WITH THERAPEUTIC DOSES H. Kakehi . Saegus. K Taten,Y d an oa Departmen f Radiologo t y Chita University Schoo f Medicino l e Chita, Japan ABSTRACT This paper describes comparative studie f uptako s effectivd an e e half-life of I in the thyroid in patients receiving diagnostic and therapeutic doses of the radioisotope. Uptake of diagnostic doses was measured conventionally. Uptake of therapeutic doses was measured using the same scintillation detector at a working distance of 150 cm and a pulse-height analyzer with a narrow window aligned on the 0.364 MeV peak in the gamma-ray spectrum. The results showed considerable indivi- dual variation meae Th n . value r 24-houfo s r uptak f diagnostio e d an c therapeutic doses were d 71.65.an 65% 'fo respectively e meath , n difference s standarit d an bein^ deffective 9 deviatioTh 5» g • % e 5 1 nhalf-lif s wa e often shorter for therapeutic than for diagnostic doses and was further shortene repeatey db d therapy e meath , n values afte d rthre onean o e ,tw therapeutic doses being 5»3 days, 4-5 days and 3.3 days respectively. concludes wa t I d that accurate assessmen e radiatioth f o t e n th dos o t e thyroid in the individual case requires direct measurement of the uptake and effective half-life. I. Introduction Whe treatmene nth t with 1-13 hyperthyroidisr 1fo n a mades s mi i t ,i important problem to know how much irradiation dose would be given to the thyroid tissues. This dose is considered to be a function of administered dos f 1-131o e , thyroie weighth f o td gland, thyroid uptak f 1-13eo d an 1 effective half-life of 1-131 in the thyroid gland. thesf O e factors thyroie ,th d effectiv e uptakth d ean e half-life wile lb discussed in this paper. In general, the thyroid uptake and the effective half-life required for determining the 1-131 administration dose are obtained from the results of the test dose given to the patients before the adminis- tration of the therapeutic dose. However, the thyroid uptake and the effective half-life would not be always the same in diagnostic and therapeutic doses. 31 recommedes i t i o S measuro t d e thyroieth d uptak effective th f 1-13eo d 1an e half-life at each time when the 1-131 therapy dose is administered. We carrie t followinou d g work. methoe Th measurinf ) o d (1 correce th g t thyroid casuptake th e n havini e a g therapeutic doss studieewa y usin b dbode th gy phantoms. e 1-13Th ) 1 (2 thyroid effective uptakth d an e e half-life were measuren o d patiente beed th ha no giveswh e therapeutith n c doses. (3) The difference between the thyroid uptakes of patients with therapeutic dose d thosan s e with diagnostic doses give ne 1-13prioth o 1t r treatmen s twa discussed. II. Methods and Results 1. Method of measuring the thyroid uptake of 1-131 in therapeutic dose. This method was established by one of our colleagues, Dr. Y.TATENO, and published in Acta Radiologica Japonica, Vol. 23,, No. 8, P. 983-986 (1963 e summarTh ) . thif o y s followss papea s i r . e therapeutiTh c dos f e administer1-13o eb o t 1 patiena o t d t with hyperthyroidism is usually 3 - lOmCi. This dose gives theoretically more than one million counts per minute, if the thyroid uptake is calibrated by the routine diagnostic methods othee th rn O hand. e resolvin,th g timf o e sealers used in most clinical laboratories is 10 microseconds at the shortest. Whe e coun th nthesn o t e sealers reache e millioon s n count minuter spe e ,th countin e totalgth losf o . s% Thereforebecome25 - 5 difficuls 1 si t ,i o t measure correct thyroid routinuptake th y eb e method whe therapeutina c dose is applied o obtaiT . correce th n t thyroid uptak regarn i etherapeutia o t d c dose countine ,th g rate shoul reducede db . A. Methods Measurin) (1 g instrument e instrumenTh t bein Departmenr g ou use n i d routinr fo t e thyroid uptake measuremen s employedtwa . a. Medical spectorometer with sealer: Toshiba ML-412 b. Crystal 0 sizecm :5 2. NalCTl x 5 )2. c. Phantom: ORINS neck phantom 32 C2) Methods of decreasing counting rate To restrict the maximum counting loss to 1%, the counting rate should be under 50,000 counts per minute with the routine counter. On the other hand 5mCf ,i f 1-13 o i 1e thyroi woulth y takee b db d p nu glan d fro therapa m y dose, the counting rate will reach about 900,000 c/m by the standard method of measuring thyroid uptake in regard to a diagnostic dose. Namely, the counting rate should be reduced to about 1/30. For this purpose the follow- ing five methods were put in trial . a. Measuring at a distance of 150cm b. Using a thicker A-filter (1.25cm Pb) c. Inserting a suitable additional cone into the collimator to make the openin ge crysta th are f ao l smaller dV pea. ke Measurink 7 £63keV5 63 + 7e ) gth e. Makin photopeae windoe th th g f o w k narrower C36keV5 4+ ) Body phantom Three kinds of body phantom with high, medium, and low body background levels were used for the experiment. Three mCi of 1-131 was put into the thyroid gland of 25ml. Assuming that the administered dose is 5mCi, the thyroid uptake would be 60%. Three different background levels of the phantom were prepare y 2mCidb , 250jaCi d OuC,an i 1-131 dose. C4) Standard source A small test tube containing 5mC f e 1-13chemicaio th n 1i l Na for f mo solution of 5ml was used as a standard source in the URINS neck phantom. Afte measuremene rth e standarth t d bod e sourcth y d phantoean m were left fodays5 3 r . Wheradioactivite th n f 1-13o y d decayee leve1ha th f o lo t d the diagnostic dose, they were measured again by the routine method. The uptake was 59.7 + 0.4%. This value was considered as the thyroid uptake rate bode th y f phantom o resulte th d s,an obtaine variouy db s method measurf so - e therapeutiinth g c dose were compared wit anothere hon discussedd ,an . B. Results Tabshow1 experimenta.e sth l results. a) Of the methods measuring at the distance of 150cm, the integral method gives a good result when the body background is low. However, if the body background is high, the uptake decreases . The correct results were obtained with differential method independent of the body background levels. 33 e methoTh ) b d usin thickea g r A-filter (,1.25cm. bring) Pb s lower values both in integra d differentiaan l l methods. c) The method inserting an additional cone into the collimator gives a lower value by differential method. In integral measurement, a correct result is obtained, whe bode nth y backgroun lows i d . However uptake ,th e becomes lower, if the body background level is high. d) The method measuring the cesium peak alone gives a lower value than the A-filter method. methoe Th ) de usin narrowea g r window cause highea s r uptake value. As the conclusion the differential method measuring at the distance of 150cm obtaine mose th dt correct value amon therapeutie th g c dose measurements by usin bode th gy phantoms. o checT k whethe bode rth y phantoms woul consideree db d similao t r patient measurementsn i s e resultvarioue ,th th f so s measuring methodn o s the 26 patients treated with 1-131 were compared with one another and are show Tabn ni . .2 Sinc correce eth t uptake valupatiena f o e unknowns i t e differtia,th l e methodistancth t a dcorrecs f 150c o eit s take mwa r tfo n answer based upon the phantom experiments. The deviations of uptakes with various measuring method tablee e showth e result ar sn Th n.i s obtained froclinicae mth l cases are quite similar to those of phantom experiments, especially those wit bod% h40 y background. Determinatio. 2 effectivf no e half-lif patienf n 1-13o i e 1 t witha therapeutic dose By the method of thyroid 1-131 uptake measurement which was mentioned in item 1 the thyroid uptake for the patients treated with 1-131 were measured chronologically. Froe datth ma obtaine effective th d e half life was determined and the results were compared with that of diagnostic dose measured before the 1-131 therapy. Then the difference in the effective half lives between the diagnostic and therapeutic doses was discussed. A. Methods (.1) Measuring instrument e sam Th ites a e 1 m 34 C2) Metho measurementf o d s Crystal-ski) i n distance In the case of diagnostic dose 40cm case Itherapeutif th neo c dose 150cm Csome time300cm- 0 s20 ) ii) Counting method DifferentiaV ke 0 3 l + countin 4 36 g method iii) Neck phantom ORINS type (3) Calculation of thyroid uptake (T.U.) P - Pb T.U 0 —————.= 10 x — S - Sb Patient': wher P e s counting rate Pb: Patient's background counts S : Counting rate of the standard source Sb: Background counts in the standard source measurement (4) Determination of the effective half-life e thyroiTh d 1-131 uptake dose measured chronologicall plottes ywa d along the ordinat semi-logarithmia n eo c graph paper against time (days) alone th g abscissa. After confirming tharelationshie tth p appear lineare b o st e ,th effective half-life was determined from the days through which the dose became one half of the initial value. ) Calculatio(5 irradiatee th f no d dose The Quimby's method was employed. The weight of thyroid gland was calculated from the Allen-Goodwin's formula, and the area of thyroid gland obtaines wa d froscae mth n image. Patient) C6 s All the cases are hyperthyroidism treated with, 1-131. The number of 196n i patient 0 9 1971- e dos 15 Th 1-13f e .eo r treatmensar 1 fo lOmC - 3 is i t at one time in each case. B. Results (1) Difference between the patients' thyroid uptakes after the administration diagnostif o therapeutid an c c doses. To all the patients treated with 1-131 a diagnostic dose was adminis- tered befor e treatmen thyroie th th d dan t uptak measureds ewa . Aftera therapeutic dose was given thyroid uptake was measured again on the same patient, and both, data were compared. The thyroid uptakes (24hrs) of 35 diagnostic and therapeutic doses in 150 patients were plotted along the ordinate and the abscissa respectively as shown in Fig. 1 to investigate the correlation between them. The dots on the graph scattered about the ° lin45 e throug origine th h t generall,bu y speaking e thyroi,th d uptakf eo a therapeutic dos s lowei e r compared with diagnostia tha f o t c dose. The mean value of the 24 hour uptakes in 150 patients with therapeutic doses is 65.6%, while that of diagnostic doses measured before the therapy is 71.5%. Tab. 3 shows the distribution of the differences between uptakes of a diagnosti ctherapeutia dosd an e casescl al e dosmea Th n .ei n e valuth f eo difference uptaken 0 casei s 15 s 5.9% i sf o s . From this resuls cleai t ri t that the uptakes of therapeutic doses are lower in general. Plotting these data, a distribution curve shown in Fig. 2 is obtained. The standard devi- ation is + 14.5%. This large value means that the differences in uptakes are dispersed. In other words, the uptakes of diagnostic and therapeutic t alwayno dose e same d therth sar san e s considerabli e e variete th n i y differences. C2) Comparison between the effective half lives of 1-131 given by diagnostic and therapeutic doses. The comparison of the effective half lives of 1-131 given by diagnostic f2) and therapeutic case1 dose 1 sees shows A n i so s n Tab n ' i nfro e . th m4 tabl effective th e e half-life obtained wit therapeutia h c dose clearlar e y shorter than that with a diagnostic dose. The mean value of the former is e latte th 6 9 daydaysd 4. 3. ran s . C3) The effective half life of a therapeutic dose and the frequency of therapy. e effectivTh e half live patientf o s s with therapeutic doses were, measure y thredb e groups ;firste thosth n ,i e second thirr ,o d group were measured in connection with the first, second or third therapy respectively. meae Th nfirse valuth tf o etherap 3 daysy 5. e grousecon , s th 5 daywa p4. d s and the third 3.3 days. There is a tendency that the 1-131 therapy dose shortene effective th s e hal fnumbee e therap th th lif s f a ero y increases. Sometimes variatioe ,th effective th f no e half life reaches several dayr fo s the same person depending on the time of different 1-131 administration. However, its mean value becomes shorter as the number of therapy becomes large. 36 REFERENCES ) TATENO(1 . Act,Y a radiol. jap (19633 ..2 ) 983. (2) KAKEHI, H., ARIMIZU, N., KASUGA, T., TATENO, Y. Acta radiol, jap(19633 .2 . ) 987. Body Background 0% 5% 40% Methods 150cm int. 59.7%* 58.5% 56.2% dif. 59.4% 60.1% 60.2% A-f ilter int. 58.9% 57.9% 57.2% dif. 55.9% 56.3% 57.5% Inserted int. 60.0% 60.0% 58.1% cone dif.57.8% 58.3% 58.8% 637 + 30 keV 56.4% 55.9% 55 . 7% 365 + 5 keV 61.3% 61.0% 61.2% Tab.1 Resultphantoe th f o sm experiment Mea* n measurment0 Valu1 f o e s True answe 59.s i r 70.4+ % , , ,, Deviationf so Methods .Uptak. .+ ,* e * 150cm int. 0% dif. - 4.2% A-filter int. - 1.7% 1.9- % dif. Inserted int. - 0.8% cone dif. - 1.0% 1.7- % V ke 0 3 + 7 63 V ke 5 + 5 36 +0.1% Tab.2 Results of the clinical experiment Uptak* e ratios calculate y 150cdb m methoV ke takee 0 r ar d3 nfo + 4 36 standards. + Mean value of 26 patients with hyperthyroidism treated with 1-131 37 - T.U.thera.(%) 1969 - 1971 T.U.diag. 24hr - 20% ~~ case4 s ( 2.7%) -% 1019 %- ~ - 15 " (10.0%) -% 9 0.1 - %^ - 32 " (21.3%) 0% -^ 9% 44 « (29.3%) 10% -— 19% 34 (22.7%) % 2029 % — - 12 " ( 8.0%) 30% ~- 39% 5 ( 3.3%) 40% ~- 49% 3 " ( 2.0%) 50% — ' 1 " ( 0.7%) Total cases (meane valuth f o e 150 cases (+5.9%) differences) Tab.3 Differences between the thyroid 1-131 uptakes of patients with diagnostic and therapeutic doses. Case E.H.L. of E.H.L. of Diag. Dose Therap. Dose 1 8 day5. s 2.4 days 2 6.5 " 4.0 " 3 4.4 " 2.0 " 4 5.7 " 4.3 " 5 5.6 4.6 " 6 3.4 " 2.5 " 7 3.2 " 2.8 " 8 5.5 " 5.2 " 9 3.5 " 3.9 " 10 4.4 " 5.5 " 11 2.6 " 5.0 " Mean 4.6 days 9 day3. s Tab.4 Effective half live diagnostif o s d an c therapeutic doses. 38 % 100 90 •t 8O 70 • * ' *. J • •/*:" *• * 60 ••.•/* o 5O « 40 30 20 10 0 JÖ 20 3O 40 50 60 70 80 9O 100% Thyroid Uptake with a Diagnostic Dose Fig 1 .Correlatio 24hre th .f no thyroi d 1-131 uptakes with diagnostid an c therapeutic doses. r25 Cases Average 5.9 i 14.5% % 60 0 5 0 4 0 3 0 0 -30-20-12 -4 0 1 0 0 Fig. 2 Distribution curve of the differences between the thyroid 1-131 uptakes of patients with diagnostic and therapeutic doses. 39 THE MEASUREMEN THYROIP TO D UPTAKE USING 99Tcm A.W.G. Goolden, H.I. Glass and E.D. Williams Department Radiotherapf so Medicad yan l Physics Hammersmith Hospital, London, UK ABSTRACT This paper survey e clinicath s l valu f earlo e y thyroid uptake tests with Tc , describes methods of carrying out such tests and presents preliminary clinical results obtained using these methods. e for th f pertechnetatmo n i Sincc T e s i trappeee thyroith y d"b d e samth e n i manne s iodidea r t doe t becombu , no s e organically bound, 99 m the early uptake of Tc is an index of the iodide-trapping function of the thyroid independent of its iodine-binding function. The 20- minut c uptakT e e a simpltes s reliabld i t an e e tes f thyroio t d carriee functionb n t repeatedl sincd ca dou an t i ,es particularli t i y y valuable in following the progress of patients undergoing therapy with antithyroid drugs. One method of carrying out the test using a dual- detector scannee measurementh r fo r f uptako t anothed an e r usinga single-detector scanner are described and their relative merits discussed. Preliminary clinical results obtained by these methods, includin e resultgth f suppressioo s n testsd carriean c t witT dou h e resultth f long-tero s m follow-up studie patientn o s s treated with antithyroid drugs e presentedar , . 1. INTRODUCTION Recent work has suggested that it is possible to predict which patients are likel o obtaiyt nremissioa n with antithyroid drug therap carryiny yb t gou test f thyroio s d function during treatment. f patiento Abou ^ 50 t s given car- bimazole and L-triiodothyronine (T3) showed suppression of thyroid uptake within x monththresi f o startinet o s g treatment (1,2). Suppressio thesn ni e patients was tested by measuring thyroid uptake 20 minutes after an intrave- 132 nous dos f o •'Ie likelihooe Th . f remissiodo hige founs b n hwa i o d t patients whose thyroid uptak suppresses ewa d under these circumstances. 41 Ther difficultiee ear interpretinn si g radioiodine uptake measurements in patients who are being treated with drugs which depend for their theraputic effec interferencn o t e with wit organie hth c bindin bees iodinef go ha n t I . claimed that early thyroid uptake measurement unaffectee sar sucy db h drugd san tha tusee b measur theo dt n yca thyroie eth d iodide concentrating mechanisr mo trap (3,4). Whethewil o this t lno s si depenratr e ro whic t th ea n do h trap- ped iodide becomes boundtime whict th e a n measuremene ,o h th n o mads d ti ean the exten whico t h organic bindin iodinf go impaires e i antithyroi e th y db d drug. Berson and Yalow (5) examined in some detail the kinetics of trap- ping and binding. They concluded from their studies that binding took place with great rapidity and that iodide once trapped became bound almost instan- taneously supporn I . theif to r readil e findingb n ca y t demonstratesi d that perchlorate prevent furthey san r accumulatio radioiodinf no thyroie th y eb d but produces no demonstrable loss of radioactivity from the gland even when given intravenously. These observations suggest that in the unblocked thyroid gland early uptake measurements are essentially measurements of iodide already bound although the earlier the measurement is made the more it will approximate to a measurement of the thyroid trap. Radioiodine can be used to measure the thyroid trap provided organic bindin completels gi y inhibited patientn I . s undergoing treatment however, organic binding is not completely inhibited. Hence a measurement at 20 minutes represents partly organically bound iodin partld ean y trapped iodide. certaint no s Ii t , therefore, wha beins i t g measure radioiodinf di uses ei n di these circumstances particularly if measurements before treatment are com- pared with measurements carrie durint dou g treatment. The studies of Ibbertson and his colleagues (6) are relevant to this problem. These workers measured thyroid clearance at varying intervals dur- firsine g th minute 0 t2 s afte intravenoun ra s dos radioiodinef eo same Th e. 42 measurements were repeated afte weekso tw r ' treatment with carbimazolee Th . earliest clearance, which was made between 0 and 5 minutes, showed no signi- ficant fall but clearances at later times did fall after treatment; the later the time of measurement, the greater the fall. This differential effect on thyroid clearance in relation to the time of the measurement is con- sistent wit knowe hth n actio f carbimazolno organin o e c binding, o t tha s i t say the later the measurement is made the more it will be influenced by organic binding. This means that a fall in the 20 minute uptake during treatment with carbimazol partle du o impairmenyt s i e f organio t c bindin thid gan s effect must be taken into account if conclusions on thyroid suppression are based on this measurement. Iffhen serial test f thyroio s d functio e requirear n d during treatment it is advantageous to use a test which measures the ability of the thyroid trao t p iodide because this functio t directlno s i n y affecte drugy db s such as carbimazole which act at a later stage in thyroid hormone biosynthesis. "Tcm in the form of pertechnetate is concentrated in the thyroid in the same way as iodide but it does not become organically bound. The uptake of this radionuclide reflect e magnitudth se thyroith f o ed trathid pan s measurement can be used as an index of thyroid activity (7). We started using Tcm primarily for the purpose of following the progress of patients undergoing treatment wit antithyroin ha d drug. Experience howeve s showha r ns i tha t i t a simple and reliable test of thyroid function and we now use it routinely in place of an early radioiodine uptake measurement. . 2 METHODS 2.1. Procedure Several workers have used radioisotope scanner r measurinfo s- up e gth take of Tcm by the thyroid (7,8,9,10). An essential part of all these methods is the correction for extrathyroidal radioactivity. Two techniques are described below, one using a dual, the other a single detector scanner. 43 The dual detector method is a modification of that described by de Garreta et William. y (10b . al (il)d al )t an e s . A fixed volume of ""Tcm-pertechnetate (0.5 to ImCi) in a syringe was counted in a mechanical jig between the two scanner detectors. Twenty minutes after an intravenous injection the thyroid scan was started. The scanner speed (approximately 90cm min ) was measured at the end of the scan. The line spacing on the scan was 0.4 cm. The maximum antero-posterior thick- ness of the patient's neck in the region of the thyroid was determined with a pair of calipers. The scan was divided into three rectangular areas. One containe e thyroidth d imagee othe beloe areaso Th on above tw r w. d on , an e e thyroith d were use o correcdt r extrathyroidafo t l activity. They were chosen so as to exclude the submandibular salivary glands and any region of high uptake belo e thyroiwth d glandnumbee Th f doto .r n eaci s h regios nwa counted using a standard cell counter. e singlth r eFo detector metho e samdth e procedur s abov a efollowes wa e d but with this metho e determined b e thyroie deptth o dth t f s o h dha . This wa s done by scanning both sides of the neck several times with the patient facing parallel to the direction of movement of the detector and seated on a chair provided wit hheaa d configuratioe restTh . e necth kf o nrequire s thae th t detector be tilted at approximately 45 so that the collimator axis passes throug e thyroidhth positio e e neck identifies e fronth Th th wa f . o f tno n do thligha e f o scat d npointe ai e collimatorwit th e hth n i routline Th f .o e the neck was obtained using a strip of lead and this, together with the scan, was used to estimate the position of each lobe of the thyroid relative to the front of the neck. 2.2. Equipment A Picker Magnascanne diametem c l 6 detectorr 7. Na witr o htw typd an se 2102A collimator uses r botswa dfo h methods. Wit e singlhth e detector method only the upper detector was used. With the dual detector method an aluminium 44 plate 1mm thic fixes e uppe kwa n fronth i d f ro t collimato pulsed ran s froe mth two detectors were fed to the dot-tapper. For calibration of the injected dose the collimators were removed and both detectors were fitted with brass plates 2.8 cm thick in order to reduce the count rate which was measured on an additional sealer. The scanner speed was measured by feeding a known pulse rate (e.g. main s e 'do t tappefrequencyth do t a factore vi r th o t )1 scaling unimeasurind t an spacingt do e gth . 2.3« Correction procedures 2.5.1« Dual detector method - Corrections are necessary to take account of variation in neck thickness and size of the scan area and changes in the scan- ner speed, because all these factors affect the scanner response. Correction r thesfo e factors eliminate necessite th s r scanninyfo gphantoa m each tima e tes s carriei t d out. The scanner was calibrated by measuring the count rate from a test dose of To contained in a plastic syringe which was positioned midway between the two detector e scanneth f mean o y sa jigthir b r f Fo o ss. procedur e collith e - mators were removed and brass discs were fixed in front of each detector. a glas n i Tsc model glan positiones dwa (volum) ml d0 3 ewit s uppehit r sur- face 0.5cm below the surface of a 20 x 20 cm perspex tank filled with water to a depth of 10 cm. The phantom was then scanned and the dots on the scan within the area enclosing the image of the model thyroid were counted. This procedur repeates wa e r varioudfo s depth numbee e f tankwateo sth Th f n i o .rr dots divided by the syringe count rate and multiplied by the dot factor was plotted on semilogarithmic paper against the depth of water in the tank. The calibration factor thus obtained (T) relates the counts in a scan to the counts obtained fro mdosa a syring f °°Tco en i m e (Pig.l) effective Th . e neck thick- lesm sc nes tha1 antero-posterioe s e takei snth b o nt r neck diamete Garrete (d r a et al. 1968). The correction for scanner speed is carried out by comparing the distance betwee a ngive n numbe correspondina e sca d f dotth o rnan n o s g measure- ment performed durin e phantogth m calibration procedure. 45 When a radioactive source is scanned, the dots on the scan are distributed over an area considerably larger than the source. In order to relate the number of dots on the scan to the amount of radioactivity in the source, all these dots must be counted. Since Tc is also concentrated in regions in the vicinity of the thyroid, it is rarely possible to select an area of suf- ficient activito siz t dot e includo e et th sdu l y eal withi thyroie nth d while excluding these other region concentrateds i s wherc T s i e t I . possible, however, to use a smaller region for dot counting, and to make a correction for the uncounted dots outside it. This correction factor (F) is the ratio of the total number of dots (i.e. those within a large area phantoa activitn e )o sourceth e numbe e mo th t th sca n ye i o ,r t ndu within a smaller area enclosing the source (Pig.2). The factor has a separate valu eacr efo h such smaller area. 2.3.2. Single detector method - With a single detector the dependence of sensitivity on thyroid depth was determined by scanning the model thyroid at several depths belo surface watere wth th f .eo These measurements were use derivo dt ecalibratioa n facto whic) user(A s estimato hwa dt coune eth t rate which would have been obtained from a thyroid at zero depth (Fig.3). 2.4. Calculatio resulte th f no s 2»4*1« Dual detector metho uptake percentaga Th ds - e a dose s th i e f o e obtained fro followine mth g expression: t X e . L . D . ) RB - 10 N 0( Uptak% ——————e= » _ — P T Ï C where = numbe N dotf ro thyroin si d are scaf ao n = numbe B dotf ro extrathyroidan si l area scaf so n R = ratio of thyroid to extrathyroidal areas = scanne D factot rdo r = coun C t rate from dose syringe 46 F = area correction factor T = calibration factor = Ke^11"^, where y. = 0.037cm"1 d = neck thickness (cm) and K = ratio of number of dots multiplied by dot factor in phantom calibration scan to ' count rate obtained from the dose in the syringe. e = correction for decay for time (t) between dose measurement and the beginning of the scan L = distance between a number of dots obtained from standard pulse rate during scan P = distance between the same number of dots obtained from standard pulse rate during calibration of phantom scan 2.4.2. Single detector method % uptake = 100 (N - RB) D. L. eXt P A PK C The symbols have the same meaning as before, except that C and K refer to count rates measured witdetectoe e correctiohon th s i r A r only d nfo an , e thyroithyroi lobet o th signia f e tw e founo s b d dar e - o th t ddepth f I . ficantly different depths then each lobe is considered separately for the depth correction. 2.5. Patients The uptake of Tcm by the thyroid has been measured in 18 normal volunteers and in 100 patients with thyrotoxicosis. For the past year this measurement has been used in all patients suspected of being thyrotoxic. To uptak s alseha o been measure patient0 3 n werdi o wh se eventually shown to be euthyroid. Most of these patients had a non-toxic goitre. Suppression tests have been carried out in 30 patients. Twenty of e patientth s were thyrotoxi somd can e were being maintaine carbimazoln do e while the test was carried out. The remaining ten patients either had a non-toxic goitr r wer o eremission i e n after treatment wit antithyroin ha d drug. The test consisted of an initial 99Tcm uptake measurement which was repeated afte e administratioth r dailweeka f 3 120|a no T r f yfo .go 47 Serial measurements of Te uptakm e have been carried out in a group of patients undergoing medical treatmen r thyrotoxicosisfo t patiente Th . s were given carbimazole in an appropriate dose with the addition of T3 SOjig daily afte e firsth r t month. Measurements were carrie t immediateldou y before and at intervals during treatment. Treatment was stopped if the Tc uptake fel o withit l e normanth otherwiss l wa rang t ebu e continuer dfo a periomonths8 1 f do . Further measurements were carrie t intervala t dou s after the antithyroid drug had been stopped. 3. RESULTS 3.1. Reproducibility of the method Measurement of the uptake of Tc was repeated using the dual detector method in 20 patients at an interval of one day wherever possible, although in one case the interval was one week, and in two cases it was one month (see Table 1). The measurements were made at approximately the same time after injectio uptakee e doseth Th f .no s rangedd froan m$ 0.8$22 o t e differencth e measuremento betweetw e th n r eacfo s h subjec uses o wa dt t estimate the standard error of the measurement, which was 0.73$> of the dose. The difference between each pair of measurements was unrelated to the magni- tude of the thyroid uptake. The error due to counting statistics (l s.d.) was 0.11??. Counting statistics are not therefore a major source of error. 3.2. Single v. dual detector Thyroid uptakes measured usin e duagth l detecto singld an r e detector methods were compared in 14 patients (Table 2). The single detector measure- ments were normally started within five minutes of finishing the dual detector measurement. When individual corrections for variations in thyroid depth are made the average difference between the uptake measured by the two methods is not significant. If a mean depth of 2.3 cm is assumed for the thyroid, once again significano thern s i e t difference between this valu thad ean t obtained detectoo usintw e gth r method preliminarA . y conclusion from this small 48 ÛO m series is that a single detector scanner can be used for measuring Tc uptake and that the estimation of thyroid depth for each individual is unnecessary. ,5*3. Uptake measurements Values for yTcm uptake in the normal subjects and in the patients with thyroid disorders are shown in Pig. 4. The mean value in normal subjects was l.ef£ + 0.7(1 s.d.). Six of the thyrotoxic patients had normal values and 7 of the patients with non-toxic goitre had values above the upper limit of the normal range. 3.4. Suppression tests The results of the suppression tests are shown in Table 3« None of thyrotoxie th c patients showe fala d uptakn i l excesn i ee th f 1*$,f o so initial uptake. In several patients the second value was higher than the n somi firsd e an caset s this differenc s significanti e . Thyroid uptaks wa e suppresse e patientth n i d s with non-toxi thyrotoxif I e th c n goitri cd ean patients who were in remission at the time the test was carried out. Accord- ing to our data a fall in thyroid uptake of at least 50$ of the initial value can be expected in non-toxic patients and using this as an index of suppression the thyrotoxic patients can be readily distinguished from the euthyroid group. 3»5. Serial measurements in patients undergoing treatment The sequential changes in Tc uptake in patients being treated with carbimazole are of interest but they have proved less powerful in predicting the outcome of treatment than was anticipated. If thyroid uptake shows a progressiv consistend an e t fal withio t l normae nth l rang e likelihooth e f do remission is high. This type of response is illustrated in Fig. 5« In this patient treatment with carbimazole and T3 was discontinued after 8 months. Withi montna c uptakT revertehd s ha epretreatmen it o dt t levels. Further tests carried out two, three and four months after stopping treatment showed a return f thitowardo d s suppressio3 en timT s e a enormalth t A n. test caused 49 the uptak falo et withi o lt normae nth l range. Nine months late uptake rth e Was still just above the upper limit of the normal range but normal sup- pressio agais nwa n demonstrable yearo Tw .s after stopping treatment this patien euthyroids twa vitrn ,ji o tests were response normath 3 d T lan o et suppression was also normal. A normal suppression test does seem to indicate a state of remission only temporarma e y b bu t i t relaps a d yoccuy an ema r withi space a nth f o e . Thiyeaso r sro sequenc eventf o e shows si Fign ni . .6 Treatment with carbimazol discontinues ewa thin di s patient afte months1 r1 reboune Th . d in uptake and subsequent suppression with T3 were consistent with a remis- sion. Thyroid remaineI statuFB d san d norma yea a afte t r rbu l fo rfurthea r six months the uptake failed to suppress with T3« Six months later the patient was clinically thyrotoxic and all thyroid function tests were indic- ative of hyperthyroidism. Patient faio achievso wh lt normaea l valu likele ear relapso yt e fairly soon but here again there are exceptions. Some patients showing this type of response have remained euthyroid for a year or more after discon- tinuation of treatment. . 4 DISCUSSION The measuremen thyroif o t d uptake using radioactive iodin bees eha n accepte simpla s usefud a ean l tes thyroif o t d function earln A .y measure- ment is more likely to reflect the rate at which the gland accumulates iodine. Since Tc is concentrated in the thyroid in the same way as iodide it is relevan consideo tt r whethe likels i t havro i advantagey t ean s ovee rth various radioactive isotopes of iodine which are currently available. The main problem associated with the measurement of early thyroid uptake is that of finding a relatively simple and convenient method of cor- rectio extrathyroidar nfo l radioactivity. Method determininr sfo g uptake by scanning depend on the net difference in dot density between the thyroid 50 and extrathyroidal regions at the time of measurement and are not based on assumptions about changes in extrathyroidal radioactivity relative to time, In a situation where the concentration of radioactivity in the gland may nogreatle b t excesn yi e surroundin th f tha o sn i t g tissue wherd e an s th e proximit e salivarth f yo y gland complicatina s i s g factor e determinatioth , n of thyroid uptake by a scanning method is probably more accurate than any other. The accurac e methoth f s ycarrieo da t presena t dou t appears adequate when use association i d n wit ha suppressio n smale testTh l . series which has been studie bot y e duasb singld hth an l e detector methods indicates that uppee th f rnormae i limith f o tl rang s raisei e dJ>.6?oo t fro 0 m3. the n this will allow for a thyroid depth of up to 5cm, which is more than twice the ave- rage depth found in our series. This would eliminate the necessity of per- m formin additionan ga l 'depth 1 scapermid nan e measuremen th t uptakTc f eo t using single detector scanners which are widely available. Other radioisotopes which giv radiatioa e n dose comparabl thao t e t whicd e suitablan earlar hn m a fro Tc r ym efo uptak e measuremenI e ar t iyz T i} -\ 2 and I (12). I, however, emits high energy gamma rays which preclude the use of a scanner and this introduces problems associated with correction for extrathyroidal activity. \7e have no experience of the comparative value of I and 9Tcm in clinical practice. 1 would be satisfactory fro mscannina radiatiod gan n dose viewpoin thit tbu s radioisotopt no s i e yet widely available. othee Theron rs ei difficult y that might arisf ei 123 the I uptake were to be measured by a scanning method. With this radio- isotop e rat th ef uptake o e wil increasee b l maintained dan lona r gdfo period because organic binding of iodine is taking place. The effect of this will bo introduct e e errors associated wit precise hth e timine measurementth f go . These error e mucsar h less importan s beini tm whegTc usen d because eth 51 •uptake has usually reached a maximum value within 15 to 20 minutes. In our experience Tc uptake measurements have proved very satis- factor clinican yi l practice absence th direca n f I o e. t comparisot ni canno saie tb d tha mory t an ethe e efficienyar t than early radioiodine uptake tests in differentiating between euthyroid and hyperthyroid indi- viduals but we think it unlikely that such a comparison would reveal any great differences. Previous experience with radioiodine tests invariably has shown that some thyrotoxic patients have a normal uptake and that a high uptak founs proportioa ei n di patientf no s with non-toxic goitre. This problem of the overlap between the two groups can usually be resolved by carrying out a suppression test. Attempt predico st e outcomtth antithyroif o e d drug treatmene th n o t basis of thyroid suppressibility have met with limited success (13,14). Suppression is not necessarily indicative of long term remission and patients who fail to suppress do not always relapse when treatment is discontinued. Despite these limitations the examination of thyroid function during treat- ment may sometimes be helpful and for this purpose a "TO uptake would seem to be the most appropriate method. REFERENCES ) ALEXANDER(1 , W.D., HARDEN McG.. ,R , SHIMMINS . ,LanceJ (1966± i t ) 1041. ) ALEXANDER(2 , W.D., HARDEN McG.. ,R , SHIMMINS McLARTY, ,J. McGill, ,D. . .P clin. J . Endocr (196?7 ._2 ) 1682. ) THOMAS(3 , I.D., ODDIE, T.H., MYHILL clin. J . , J Endocr 0 (i960.2 ) 1601. ) KDUTRAS(4 , D.A., SPONTOURIS Endocr. J . ,J . _3j> (1966) 135. ) BERSON(5 , S.A., YALOW, R.S clin. .J . Endocr (19554 ._3 ) 186. ) IBBERTSON,H.Z.(6 , HÜNTON, R.B., WHITE McL.. ,B , GLUCKMAN, P.Dn I . Proc Internationah .6t l Thyroid Conference, Vienna (1970). (7) ANDROS, G., HARPER, P.V., LATHHOP, K.A., McCARDLE, R.J. J. clin. Endocr (1965£ .2 ) 1067. 52 (8) SHIMMDTS, J., HILDITCH, T., HARDEN, R. McG., ALEXANDER, W.ü. J. clin. Endocr. 28 (1968) 575- (9) ATKIMS, ÏÏ.L., RICHARDS, P. J. nucl. Med. _9 (1968) 7. GARRETAE (10D ) , A.C., GLASS, H.I., GOOLDEN, A.W.O. Brit . Radiol.J . 41 (1968) 896. (11) WILLIAMS, E.D., GLASS, H.I., AHNOT, R.N., DE GARRETA, A.C. In "Medical Radioisotope Scintigraphy" _!, International Atomic Energy Agency, Vienna (1969N' p.665. (12) GOOLDEW, A.¥.G., GLASS, H.I., SILVESTER, D.J. Brit Radiol. .J . _41 (1968. )20 (13) ALEXANDER, W.D., McLARTY, D.G., ROBERTSON , SHIMMINS,J. , ,J. BROWNLIE, B.E.W., HARDEN, R.M., PATEL, A.R. J. clin. Endocr. ^0 (1970) 540. (14) LOWRÏ, R.C., LOWE HADDEN, ,D. , D.R., MONTGOMERY, D.A.D., WEAVER, J.A. Brit .(1971? j med . . J .)19 53 Table 1 REPRODUCIBILITY OF UPTAKE METHOD NO. UPTAKE% UPTAKE% MEAN UPTAKE ABSOLUTE DIFFERENCE DIFFERENCE AS % MEASUREMENT 1S T 2ND MEASUREMENT BETWEEN UPTAKE% S OF MEAN UPTAKE 1 12.7 13.0 12.9 0.32 2.5 2 1.8 1.5 1.7 0.25 15 3 3.6 3.6 3.6 0.03 0.8 4 6.9 6.5 6.7 0.34 5.1 5 8.9 8.8 8.9 0.06 0.7 6 8.0 7.0 7-5 1.04 14 7* 6.7 5.4 6.2 1.29 21 8 10.9 12.0 11.4 1.17 10 9* 4.5 4.8 4.7 0.3 6.5 10 22.3 21.2 21.8 1.1 5.1 11* 4.5 4.8 4.7 0.24 5.2 12* 7.9 6.7 7.3 1.22 17 13 2.1 1.4 1.7 0.74 43 14 3.9 2.8 3.3 1.18 35 15 1.1 0.8 0.9 0.30 33 16 5.0 5.8 5-4 0.78 15 17 9-7 9-6 9.6 0.05 0.5 18 1.6 1.3 1.4 0.37 26 19 8.4 9.4 8.9 0.99 11 20 5-9 4.0 4.4 0.85 19 intervae Th * l between day9 thes2 sdays6 2 3 e1 daysmeasurement6 o 1 days,3 N 1 2 9 o ,7 o N , N o N : mors sy wa e da thae non Table 2 COMPARISO UPTAKEF NO S USING DUA SINGLD LAN E DETECTOR SCANNER METHODS NO. DUAL DETECTOR SINGLE DETECTOR DIFFERENCE FROM DUAL SINGLE DETECTOR DIFFERENCE FROM METHOD METHOD WITH DETECTOR RESULT METHOD USING MEAN DUAL DETECTOR INDIVIDUAL DEPTH m c 0 DEPT2. F HO RESULT CORRECTION 1 7.6 7.2 - 0.35 7.0 - 0.59 2 2.0 2.0 + o.ok 2.0 - 0.0k 3 1.9 2.1» + 0.56 2.3 + o.ko k* 18.7 2k. 3 + 5.7 20.6 + 1.95 5 1.3 1.2 - 0.07 1.2 - 0.05 01 Ul 6 9.6 8.7 - 0.88 9. k - 0.25 7 2.6 2.1 - 0.5U 2.1 - 0.1*7 8 It. 8 5-7 + 0.92 5.5 + 0.7!* 9 5.3 5.^ + 0.0k 5-7 + 0.32 10 1.8 1.5 - 0.31 1.5 - 0.32 11 1.0 1.2 + 0.27 1.3 + 0.30 12 5.5 k.9 - 0.63 It. 8 - 0.75 13 2.5 2.7 + 0.15 2.7 + 0.20 Ik 21.lt 20.6 - 0.82 20.9 - 0.5 MEAN (absolute) 0.79 0.38 thin I s* casmeasuremente eth minute8 s3 werd an s e 7 afte2 don t ea r injection moss i tt I probabl. e that the uptake was still increasing during this time. This result has been excluded in calculating the means. m TABLE 3. T3 SUPPRESSION TESTS USING UPTAKE MEASUREMENTS PATIENT EUTHYROID PATIENTS 99Tcm UPTAKE (%) PATIENT THYROTOXIC PATIENTS 99Tcm UPTAKE (%) BEFOR 3 ET AFTE3 RT BEFOR3 ET AFTER T3 1. B. K. 0.9 0.1 9- A.C. 1.7 1.9 2. H.W. 1.0 0.0 10. A. H. 1.8 2.1 3. L. P. 1.4 0.2 11. M. N. 2.0 2.2 h. A. S. 2.1 0.7 12. C.M. 2.1 3.1 5. B. P. 3.0 o.i* 13. S. L. 2.2 1.9 6. ) Z.B(i . 3.3 0.3 14. A. T. 2.3 2.3 Z.B. (ii) 4.1 o.i* 15. R. K. 2.3 1.9 Z.B.(iii) 5.0 1.6 16. P.E. 3.1 4.5 7. B.C. 8.1* 1.7 17. A. G. 3.5 3.0 8. C.H. 8.6 2.0 18. A. H. 3.8 3.5 19. J.K. 5.0 1*.2 20. S.O. 7.5 7.0 21. S. N. 7-5 7.2 22. M. H. 8.3 9.4 23. A. L. 8. U 7.4 2k. A.B. 9.0 8.9 25- B. T. 12.0 15.3 26. M. A. 17.0 23.0 27. B. H. 18.9 21.4 28. V. H. 22.2 20.8 CORRECTIO NATTENUATIOR FACTOFO ) (T R N E TJECTH KY B (DUAL DETECTOR METHOD) 1.2 1.1. 1.0. 0.9- 0.8- 0.7 m c 8 1 6 1 U l 2 1 0 1 8 Heck thickness FIGURE I Correction factor (T) for attenuation by the total neck thickness (dual detector method). 57 DEPENDENC CALIBRATIOF EO NAREE TH FACTO AN O RF WITHIN WHICH THE DOTS ARE COUNTED 1.00-T 0.95- (RELATIVE VALUE) 0.9QJ 50 75 100 125 150 175 2 AREA ON SCAN WITHIN WHICH DOTS ARE COUNTED cm FIGURE 2 Dependence of the calibration factor (P) on the e scaareath nn ,o withi n which dote countedar s - 58 CORRECTIO NATTENUATIOR FACTOFO ) (A R N BY TISSUES OVERLYIN THYROIE GTH D (SINGLE DETECTOR METHOD) 1.0 0.9- 0.8- o.r 0.6- 0.5- 0,1*. m c T IC .Mean thyroid depth FIGUR 3 E Correctio nr attenuatiofactofo ) (A r tissuey n"b s overlying the thyroid (single detector method)« 59 40 ui 30 * û. I *> I .o IM* U O) :F ir. NORMAL i. i* RANGE Ü!' NORMAL NON-TOXIC HYPERTHYROID GOITRE PICTUR 4 E Value r "Tcfo s * uptak v i normae l sx-.bjects (18). Patients with non-toxio goitres (30). Patients with thyrotoxicosis (lOO). 60 _ 15 o o 10 Carbimazole V////W/////////////////////A T ______i 3 '.:.>..:....,::3 '- •'""-- ' . 10 10 12 MONTHS FIGURE 5 Serial 99 Tc ni uptake measurements in a patient during and after treatment with carbimazole and T3. This patient was in remission two years after stopping treatment. 61 20 E O O -«^ 10 ö> NORMAL RANGE CO o: CARBIMAZOLE T3 CL D ce 10 'NORMAL RANGE_ an cn 5 2 0 2 5 1 10 30 35 MONTHS FIGURE6 Serial 99 Tc" i uptake measurements in a patient durin afted an g r treatment with carMmazole and T3. Suppression was demonstrable in this patient at the time she stopped taking cartimazol e relapsesh t bu ed abou 8 month1 t s later. 62 THE MEASUREMEN THYROIE t TH a P I DO T UPTAK d "F an mO E Tc I , EARLY TIMES AFTER ISOTOPE ADMINISTRATION J.G. Shimmin d ¥.Dan s . Alexander Western Regional Hospital Board Regional Departmen f Clinicao t l Physic d Bio-Engineeringan s ; University Department of Medicine Gardiner Institute, Glasgow, Scotland ABSTRACT This paper describe methosa d usin gsingle-detectoa r scanner for measuring the early uptake of Tc , I or I by the thyroid. The method was tested "by comparing the uptake values obtained in 16 subjects on five occasions during the 45 minutes following administra- tion of the tracer with those obtained on two interpolated occasions y meana fixeb f o sd collimated scintillation detector fitted witha standard thyroid collimator. In only one case was there a significant difference betweeo set tw measurementsf o se th n s showwa t nI .tha e th t I activity detected with the fixed detector was equal to that in a 15.8 cm diameter circle on the scan. The method described also permits the measuremen extrathyroidaf o t l activity. Froe resultth m f suco s h measurements mean values for the extrathyroidal Tc and I activity detected by the fixed detector at different times after admin- istratio e traceth f ro n were calculated. These values were useo t d formulate equations from which the early uptake of these radionuclides calculatee b n ca d from measurements wite fixeth h d detector f shortagi , e of time or other considerations preclude the use of the more accurate scanning method. When studying the concentrating mechanism of iodide or pertechnetate (the iodide trap), it is important to measure thyroid uptake at early times after tracer administration, fit these early times it is possible to separate the concentrating and the chemical organification (binding) mechanisms of the gland (1-4) The activity of tracer in the neck u/hen viewed by a standard uptake counter is distributed in thyroidal and extra-thyroidal regions. In 63 investigation f thyroio s d gland uptake soon after radioiodide administration correction for the extra-thyroidal activity is of particular importance. At these early times the extra-thyroidal activity is at a maximum and the thyroidal activity is at a minimum. This correction for extra-thyroidal activit s easili y y made usin isotopn a g e imaging system. The e tracenth r glane th s easil i dn i y identified. Therefor n thiei s pape e describw r e a method of measuring the thyroid uptake of Tc and I using a conventional scintiscanner e resultinTh . g measurement f extrathyroidaso l activity in th.e field of view of the standard collimator ' have been used as a basis of a method of measuring tracer uptake using an uptake counter. This latter method is used in circumstances where a large number of patients are to be studied, or where a scintiscanner is not available. The Use of a Scintiscanner to Measure Thyroid Uptake IHethod A tracer dose of 25-50 |_iCi of I or 1 mCi of Tc is intravenously administered. Either a Picker V magnascanner (50 uCi 131 I) or a Selo 131 DS 4/4 scintiscanner (25 ^Ci I) are used to scan the subject. Scanning s startei y timan et c aftea daftese 0 r3 r tracer administration linA . e 0 cm/mi speea s use10 i d f m an dspacino nm 2 cm/mi 7 (Picke8 r f o o g n ) V r (Sel aree S 4/4)Th oD a .scanne d starts just abov thyroie th e d gland an d extend belouo t s sternae )th l notch scae s completeTh min4 ni . - . 2 n i d e pulsTh e height o detecanalyset scanne e t th se t f pulses ro ri s equivalent to the energy range 310 - 410 keU for 131I and 120 - 160 kel/ for "mTc. In each case a broad focus collimator is used with a focal length of 12.5 cm. In every case the dot factor is adjusted so that all the dots are clearly resolved. 64 A 'box* is drawn round the thyroid on the scan. This box if of such dimensions that it just covers all the thyroid uptake. A second box is drawn just beneath this box, with the same width and enclosing two scan lines. The number of counts in each box are summed. The extrathyroidal activit secone e count thyroie s take th th th i x time x n n s bo dsi i ya n bo d s halscae th f n firse lineth tn si box . This backgroun s subtractei d d from the counts in the thyroid box to give the thyroid counts. After scanning the subject, a thyroid phantom, similar to the I.A.E.A. phantom but •filled with water s scanne,i d containin aliquon injectioe a g th f o t n activite solutionphantoe th th o t n e doti ye m Th .du sthyroi e thear dn uptake th l countee al count d e expressean d ar s percentaga s a de th f eo •phantom1 counts. Justificatio f Backgrounno d Area Two subjects with no thyroid uptake were studied to determine how satisfactor chosee th y n background area was r thes Fo .o patient tw e s with no thyroid uptak meae th en difference betwee true th ne backgroune th n i d estimatee th d thyroian dx bo background d usin s nearle seconwa th gx ybo d zero 131 Relationship of Scanning Method To Uptake Counter - I In order to relate the scintiscan uptakes to those measured using a standard I.A.E.A. collimated uptake counter, 16 subjects were scanned after bein t drathin no ,I g ws d e scans. boxegivestuddi I th e t n ui snyi ,bu 131 constructed circles firse Th .t circl n diamete15.s i ewa m 8c d an r represented the average sensitive volume viewed by the collimated counter^ . s approximateli 15.m c 8 crose th y s sectional diamete neckdepthd mi t a re Th . 65 end of the collimator is 8.5 cm from the surface of the neck. The neck diamete backgroune Th s assume i r. 13.e b o 0dm t d c counts were founy b d (7) countin sema e dot n th gii s circle area underneat circle th h f diameteeo r 15.8 cm. Scans mere made at five intervals during the first 45 min after tracer administratio uptakd an n e countn usinmi g4 s1 merd an e 7 mad t a e a Nal(Tl) crystal with a standard thyroid collimator^ . Result^of Comparison Fig show1 . measuremente th s necf o sr eac kfo h activitI f o y 131 patien s recorde a tscannee th y b dcollimatere th (Us d )an d scintillation counte injectionI e aften rar e mi valuee s (Ucth r7 U Th .t f )a o s 131 derived from the best fit curves drawn through all the data for each patient. The results show that there was a significant difference between Us and Uc (that is a difference greater than three standard deviations) for only one patient. Similar results were found at 14 min after 131I administration . Measuremen f Neco t k Extrathyroidal flctivity have W e show ns possibli tha t i t e froscintiscae th m measuro t n e th e extrathyroidal activity plus the thyroidal activity. UJe have already outline methoa d measuro t d e thyroith e d uptak hencd s possibli an e t i e e by subtractio measuro t n extrathyroidae th e l activity detected usine th g collimated thyroid uptake detecto . Thibees r sha n donI botr fo eh and mTc at times up to 36 min after intravenous administration of the resulte Th showe tracefigsn . sar i n ' .r 2-5(7 8extrathyroidae ) .Th l activity is expressed either as a percentage of the dose given or as a thyroide th percentag n i dos e .t th eno f eo 66 Discussion seee b 5 fign thani n 2- Isca tt ther s considerablei e variation ni the neck extrathyroidal activity. Even when this activit s expressei y s a d a percentage of the dose given which is not in the thyroid, a variation of aften dosI mi s founr3 ei isotopt f a do $ 11 e o administratiot 4 a d an n 131 variation of 3.5 to 9% of Tc at 3 min after the intravenous administration of Tc. These percentage activities are considerably larger than the n aftemi 3 rnorma t administratioa lc T thyroi d an d I an nuptake f o s s cleai t thyroii e r th tha f i td uptak f iodideo e b tracero t e ar s measured accuratel t thesa y e early time intervals isotopn a , e imaging system mus usede b t . Often, howevere th t feasibl, no o thit s e si du e large number of patients, the amount of data processing required with imaging systems and the availability of a suitable imaging system. Therefore lue have used the average values found for the neck extrathyroidal activity standara see y b n d thyroid uptake counte o formulatt r e equations to measure thyroid uptake using an uptake counter. These equations are based largelrate f falth eo f extrn lo o y a thyroidal activity. Fig6 . shoufs this rat f faleo l compared witrate th f hfaleo f plasmo l a activity in one subject. It can be seen that the rate of fall of extrathyroidal neck activity (expressed as a percentage of the activity given) falls at a much slouier rate than plasma activity e averagTh . e rate th f faleo f lo 131 extrathyroidal activity of I (expressed as a percentage of the dose not in the thyroid) ujas found to be 14% between 2 and 20 min. The average value of extra-thyroida n aftelmi activit2 r t n thyroida i dos% % t ( 1 y eno s )wa administration. Hence If the neck uptake at 2 min is greater than 1%: Neck uptake 2 min = Thyroid uptake 2 min + 7/100 (100 - Thyroid uptake 2 min), i.e., Thyroid uptake 2 min = 1/0.93 (Neck uptake 2 min - 7), Neck uptake 20 min = Thyroid 67 uptake 20 min + 6/100 (100 - thyroid uptake 20 min), i.e., Thyroid uptake 20 min = 1/0.94 (Neck uptake 20 min - 6.0). If the neck uptake at 2 min is less than 1%' Neck uptake 2 min = Extrathyroidal activit min2 y , Neck = Thyroiactivit n mi d0 2 yUptak e min/10 2 86/10+ A n ET mi (100x x 0 02 Thyroi- d uptak min)0 2 e , i.e., Thyroid uptake 20 min Neck uptake 20 min - 0.86 Neck uptake 2 min % dose. 1 - 0.0086 Neck uptake 2 min The equivalent equations using Tc are found as follows:- The mean Tc extrathyroidal activity is 6.65$ of activity not in the thyroid at 3 min and 5.46$ at 20 min. Then the thyroid uptake of mTc is calculated as Neck uptake Thyroid uptake of "mTc c T of~ 99mT amin(U33 t ) at 3 min (T3) 6.65(100 - T3) 100 i.e. Thyroid uptake Ü3 - 6.65 dose n mi a3 t 0.934 At 20 min: Neck uptake Thyroid uptake _ 99m... c T f o „ 99m_ of Tc at 20 min (U20) at 20 min (T20) x (100 - T20) 68 i.e. Thyroid uptake * 99m_ (U2 D5.46- , )_ V 0.945— = dose* — ' c T of n mi 0 a2 t If the neck uptake at 3 min is less than 6.65$, me must consider tha l extrathyroidat al thi s i s l activity and the thyroid uptake is negligible. Then U20 = T20 + U3 x 0.82 x (100 - T20)/100 % dose. i.e. Thyroi= n dmi uptak0 2 t a e . (U2, - 00.8- ) U3 2x (1 - 0.82 LJ3/100) % d°Se These equations haue been use o studt d larga y e grou f patiento p s where sequential measurements of thyroid uptake of Tc and I are made at 2 (9) aften mi anr0 d2 administratio . Thin s study involved tuio approximations equatione th f o s 1 13 132 (l) The use of I rather than I and (2) The use of 2 min Tc uptake rather than 3 min 99m , . TTc uptake. Hoiuever, when sequential measurements are made, it is likely that errors arisininnaccuracieo t e gdu n measurini s g thyroid uptakee ar , eliminated in the comparison of uptakes. REFERENCES (1) WOLPP, ,T., Physiol. Pev. 44 (1964) 45- (?) BEESON, S.A., YALOW, R.S. .T. clin. Invest. _3_4 (1955) J8 (3) TNGBAR, S.H. Trsns. Amer, goiter Ass. (3953) 387. (4) TNGBAR, S.H. J. clin. Endocr. ]Jj (1955) ?38. ) (5 BEIßHER, E.H., GOMEZ-CRE?Pn , TROTTG. , , W.O., VETTE1R. H , Îîucl.-Med. (Stuttg.) 4 (1964) 78. 69 (6) INTERNATIONAL ATOMIC ENERGY AGENCY, Brit. J. Radiol. yj (196?) ?0% ) ÏÏILDITCÏÏ(7 , T.E., GILLESPTE, F.C., SHTMMINS , J. HARDEN, . McG.R , , ALEXANDER, W.T) . J r.ucl. . Med 8 (1967. ) 810. ) (8 SHIMMINS , J. ÏÏILDITCÏÏ, , T.E., HARDEN . Meß.R , , ALEXANDER, W.D. . J nucl. (1969'Med> K . ) 483. ) (9 SÏÏIMMINS , J. ALEXANDER, , W.D., McIARTY, D.G., ROBERTSON, J.W.K., SLOANE, D.J.P. J. nucl. Med. 22 (2312} 51. 9 UPTAKE COUNTER APPARENT NECK ACTIVITY 2 1 9 6 3 SCANNER(15-8cm d) Fig. 1 A comparison of total neck activity as measured by the scintiscanner (15. standarcirclem e c 8th d )an d uptake counter. ^ 70 ETA dose 10 T 8- 6- 4- 2- 0 3 8 2 6 2 4 2 2 2 0 2 8 1 « l M 2 1 C 1 8 6 4 2 Time after Injection (mina) Fig. 2 Relation between the contribution from extrathyroidal neck activity /•lii and time after administratio e radioisotopth f o n 6 patients1 n ei .V CorrecteA dET V. do.« »1 A A 0 3 8 2 6 2 4 2 2 2 0 2 8 1 U 4 1 2 1 0 1 8 6 4 2 Time after Injection (mins) Fig. 3 Relation betuieen the contribution from extrathyroidal neck activity (as % dose not in thyroid) and time after administration of the radioisotop patients6 1 n i e .\ -*-/ f'4'f ) 71 E.T.A.WmTc , Dote Administered) 8-1 6- 4- 2- i i i r i i i i i ~ 6 3 8 2 0 2 2 1 4 TIME after INJECTION (Min) 99m, Fig. 4 Best-fit line to component of extrathyroidal activity of see thyroiy b n d collimator. Extrathyroidal activit 6.7y= 7- 0.25 t + 0.108t2 _ 0.00016t3 % dose (t in min). E.T.A. »»m of TOTAL BODY E.T.AJ* 6- 4-J 2- 4 12 20 28 34 TIME after INJECTION (Min) Fig. 5 Best-fit line to extrathyroidal activity of Tc expressed as percentag f total-bodeo y extrathyroidal activity. Extrathyroidal activity = 7.09 - 0.16t + 0.005t2 - 0.00006t3 % body extrathyroidal activity (t in min). 72 .ETA PLASMA ACTIVITY % dose % dose/ml 10- r-02 r -01 0 3 6 2 2 2 8 1 4 1 0 1 34 38 42 Minutes after Injection Fie). 6 Relation for one patient between ETA (% dose) and plasma activity l »7 1 (% dose/ml) and time after administration of 500 (jCi I. ETA: triangles between parallel lines. Plasma Activity: triangle circlesn si . 73 THE MEASUREMENT OF THE KINETIC CONSTANTS DESCRIBING THE THYROIDAL CONCENTRATIO ORGANID NAN C BINDIN IODIDF O G PERTECHNETATD EAN E J.G. Shimmins, J.W.K. Robertson, W.D. Alexander and J. Lazarus Western Regional Hospital Board Regional Department of Clinical Physics and Bio-Engineering; University Departmen Medicinf o t e Gardiner Institute, Glasgow, Scotland ABSTRACT This paper describes studies of the kinetics of iodide-trapping and iodine-bindin e thyroith y gb n norma i d hyperthyroid an l d subjects based on computer analysis of the data resulting from serial Tc and I uptake measurements made with a single-detector scanner minute5 durin4 e gth s followin e administratioth g e mixeth f do n tracers. Studies were carried out on 10 normal and 4 hyperthyroid subjects to whom carbimazole had been given to block iodine-binding e thyroidbth y . Analysi f theso s e data yielded e univalueth r - fo s directional iodide clearance into the thyroid and the fractional iodine-binding rate. Further studies were carried out on 15 normal an 7 hyperthyroid d subject o whot s carbimazolo mn d beeha en given. Analysi f theso s e data yielded e unidirectionavalueth r fo s l iodide clearance inte thyroidth o e fractionath , l iodide loss rate froe th m thyroid and the fractional iodine-binding rate. The results indicate a very significantly higher unidirectional iodide clearance and a significantly higher fractional iodine-binding rate in hyperthyroid s comparea d with normal subjects significano N . t differencen j s fractional iodide loss rate observes wa s d betwee e groupth n s studied. The significance of the findings is discussed. Introduction Inorganic iodide is concentrated from blood by the thyroid gland. In the normal thyroid this iodide is organified and cannot then be discharged (l 2) by perchloratobservee Th . d ' thyroie dobservee uptakth d an ed plasma clearanc f radioiodino e e thyroith y b e d gland depene d th bot n o h concentratio e organificatioth d an n n mechanism. Certain anti-thyroid drugs (e.g. carbimazole ) e correcgiveth n i n t amount hoiueveo d s r eliminate th e 75 organification of iodide in the thyroid. The uptake and loss of radio- (1 2) iodid then simple ca eb n y attribute concentratine th o t d g mechanis' m and is similar to the uptake and loss of the pertechnetate ion which is also concentrated by the thyroid gland (3). The measurement of the unidirectional clearance of pertechnetate into the thyroid and its loss froe thyroith m s beeha d n mad y graphicab e l analysi e thyroith f o sd uptake plot of pertechnetate . In the same may it is possible to measure the unidirectional clearance of iodide due to the iodide concentrating mechanism and the intrathyroidal loss rate of iodide provided carbimazole s givei preveno t n t thyroidal organificatio f iodideo n . In addition to the measurement of the accumulation and the loss rate of iodide, with organification blocked, we have made an analysis of the thyroidal iodide uptake curve and have found the best fit kinetic constants. This analysis was made using a digital computer and evaluates the unidirectional clearance, the loss rate and the binding rate of iodide. A Materials and Method (Carbimazole Studies) Fourteen subjects were include n thii d s study. Clinical detailf so these subject show e n werar s Te n tablni e . euthyroi1 e foud an dr were thyrotoxic. All the subjects were given 120 mg of carbimazole divided into four doses over 24 hours, the last dose being given one hour before the test c pertechT m f o - i startedmC 1 d .an I Each f subjeco i gives uC twa 0 5 n netate by intravenous injection without any iodide or pertechnetate carrier. c pertechnetat T e thyroiTh d an d I uptakee werf o s e then fount a d several times after isotope administration. These thyroid uptakes were measured using a Picker V magnascanner, by making successive scans of the thyroid region . Each scan took approximately three minutes and it was found possible to complete at least nine scans in the first 45 minutes after 76 isotope administration. Tuio set f scanso s were made e firsTh . t scan urns done under Tc counting conditions (detecting pulses equivalent to 125 131 5 keU)t15 o secone .Th d scas donwa n e undecountinI r g conditions 99m 131 (detecting pulsescaI n0 keV) s42 d equivalen.an o t c T Eac0 30 h o t measured the thyroid uptake at the mid time of the scan. Alternate scans mere made to measure the pertechnetate and iodide uptakes. The dots on the scintiscans were converted to percentage uptakes of the administered dose by counting the dots in selected parts of the scan relating these dots to e dotth s produce y scanninb d n aliquoadministeree a g th f o t d a dos n ei standarI d thyroi o t c scae T d du nphanto e . Alsth dote mn th oi s 131 mere estimate y countinstandarI b d same th e n n a gthyroii d d phantom under both 131 I and 99mTc scanning conditions. Blood samples iuere taken at 2, 8, 15, 30 and 45 minutes after isotope administration. These blood samples mere separated and 2 ml of serum from each sample mere counted in n automatia c well l\lal scintillation counter (*l\luclear Chicago Mode. No l 4227). This instrumen spectrometeo tw s ha t r channels channee On .s wa l e energth o detecn t yi t I rangtse pulse ed equivalenan sc T fromo t t 131 100 to 180 keU. The second channel was set to detect pulses from I in the equivalent energy range of 300 to 420 keU. These serum activities were converted to fractions of the dose administered by counting a diluted 2 ml aliquot of the injected solution. Also a 2 ml aliquot of 131I counts in c countinT the g channel. Calculation (Carbimazole Studies) e analysi uptakTh e th plasmd f an eso a dat o measurt a e unidirectional clearance and intrathyroidal loss rate has been fully described in a (4) previous communication . 77 Essentiall t dependi y s upofollowine th n g differential equations describing the rate of change of thyroid uptake of I or mTc. dqt dT~ = - kTB ' qt + C'qs = Thyroiq d uptak dose% ( e ) q = Serum activity (% dose/ml) 5 kTR = Fractional loss rate from the thyroid (min"" ) C. = Unidirectional clearance into the thyroid (ml/min) 1 dqt qt ' C + ~ q B T k ~ = T d q Hence ^s s t q t dq I Therefor plottes i — — — f dei againsstraigha — t t line Q ut Q be found mit ordinathd slopan q mer d ek ean intercepfoun — — d . C t D T l D dt t froe thyroith m d uptak eq foun plod an td froe seruth m m activity curve S r bot. fo Tc h """" d Ian n comparinI e accumulatioth g f iodido n pertechnetatd an e e inte th o thyroi unidirectionae th shale w de lus l clearance. This serum clearance is the rate of iodide and pertechnetate uptake into the thyroid. Results (Carbimazole Studies) The thyroid uptakes and plasma activities were plotted as shown in figs. l(a) and (b). Tangents were then drawn to the uptake plots and C. m anfoun k- dr eac fo dh subject usin calculatioe th g n described. These I o values are shown in table 1. The thyrotoxic subjects show large clearances and henc meao en n valu unidirectionae th s giveei r fo n l clearancen I . every subject except 30 the iodide unidirectional clearance is greater than the pertechnetate unidirectional clearance. The relation between these two clearance showe bese lint ar s Th fign thesfi o ti nt e . .2 e dat: is a 78 + 50. = 70.84C .. J . C 5 icu^ equ. 3 . The best fit line through the origin is given by: C.j = 1.586 C. equ. 4. Both these lines are severely affected by the values of subject GO. ( Tc Unidirectional Clearanc ml/min)9 32 = e. The mean ratio of the two unidirectional clearances shown in table 1 is 2.20 (SEM 0.29). No significant difference UJas found betuieen the k_D of I D pertechnetat iodidd an e n eitheei normae th r r thyrotoxio l c subjects. B lYlaterials and Methods (Binding Studies) Twenty-two subjects were studied. Fifteen were hyperthyroid and seven u/ere euthyroid. A dose of 25 uCi of 131I as iodide was given by intravenous injection. Venous blood samples were taken at 2, 8, 18, 35, 105 and 150 minutes after injection. Serum aliquots were counte n automatia n i d c well scintillation counter with the pulse height analyser set to cover the range 320-390 keU. A standard containing an aliquot of the dose was counted together with the samples, and the sample activity was expressed administeredI percentaga s a e th f o e . 131 The thyroid uptak measures wa e d usin 4 scintiscanner 4/ Sela g S D o . The technique used was similar to that previously employed to measure the thyroid uptak iodidf eo pertechnetatd ean . e Calculation (Binding Studies) The open three compartment model is shown in Fig. 3. The fundamental equations describing the material balance in this model are dIT dT = C'IB ~ kTB-ZT ~ "V1! dlb dT = kbJT 79 These equations may be solved for I (TOTAL), the total thyroidal 131I (7) activity . Values of C, kbD , and kTiD b are then inserted until the best fit is found between the measured uptake values and the solution of the equations. These values of C, k and k are then the best estimate of bn TIO b these kinetic constants. The thyroid radioiodine uptake has been analysed in the 15 thyrotoxic and 7 euthyroid subjects. The analysis was performed using an 8K PDP8-I computer (Digital Equipment Corporation) with a programme writte n FOCALi n . Results (Binding Studies) The results are presented in Table 2 and a typical result is shown in Fig. 4. All the hyperthyroid subjects had greater unidirectional clearance valuee euthyroith f so thay d an nsubjects e meaTh .n hyperthyroid unidirectional clearanc s n 196.wa mi comparee l 0m o 36.t d r minl 8m fo ~ euthyroid subjects. The difference is significant (p <0.00l). The mean binding rate k, in the thyrotoxic subjects (0.110) is significantly greater than in the euthyroid subjects (0.066) (p <0.025). There is no significant difference between the mean exit rate kTO in the two groups I D (p> 0.05). Conclusions e importancTh f theso e n scarcitei date li af othe o y r measuremenf o t (2) these kinetic constants. Berso Yalod an n w have however measuree th d unidirectional clearance and the k of iodide in a group of thyrotoxic TID b subjects. They found a mean value of 337 ml/min for the unidirectional clearanc f thio f iodidseo k grou0.3 d e an ef thyrotoxith o p8 minr fo ~' c I b subjects. One normal subject had an unidirectional clearance of 40 ml/min 80 -l (4) and a kTD of 0.047 min . Shimmins et al. haue measured the l D unidirectional pertechnetatf clearanco T k d groua an e n hyperf ei o p - thyroid and euthyroid subjects. Mean values of 287 ml/min for the clearance and 0.088 min for kT were found in the hyperthyroid group. lD e euthyroiTh d subject meaa d n ha svalu f 36.o e 8clearance ml/mith r fo n e and 0.08 k3e meae T0value th minth .n Th r f unidirectionao e"fo l I D clearanc pertechnetatf eo epresene founth n i dt stud f 32.o y 1 ml/mir fo n the euthyroid subject s thereforsi e near previouou r s findings. The mean value of 64.7 ml/min for the euthyroid unidirectional clearance of iodide (Carbimazole studies) is higher than the unidirectional clearanc ebindine founth n i dg studies (36.8 ml/min). Botmuce ar hh higher /g\ than the net iodide thyroidal clearance in euthyroid subjects (22.6 ml/min). This difference may be due to the type of analysis, the f carbimazolo e differenus e th r eo t partients studied. Whesame th ne analysis s appliebindine wa th s a o ,t dg studie s appliee wa sth o t d (g) carbimazole studies, similar values were foun . Henc valuede th e s obtained are independent of the analysis method. The ten patients given carbimazole were repeated without carbimazole and the pertechnetate kinetic parameters found. Although the values mere reduced, the differenc significantt no s ewa e differencTh . mea e th n n e valueei th f o s iodide unidirectional clearance may then be due partly to the use of carbimazole to block binding and also partly due to the different selection of patients studied. e exiTh t rate constant k-,-,-r iodidf° , s alsewa o highee founb o t dr I Id in the carbimazole studies (0.059 min~ compared to 0.030min~ ). This difference was however, not statistically significant. 81 EEFERECCES ) WOLFF(1 . ,J Physiol . Rev (19644 ._4 « )45 (2) BERSON, S.A., YALOW, R.S. J. clin. Invest. _34 (1955) 186. ) SHIMMINS(3 , HARDEN,J. McG.. ,R , ALEXANDER, Vf.D nucl. .J . Med. 10 (1969) 637. ) SHIMMINS(4 HILDITCH, ,J. HARDEN, ,T. McG.. ,R , ALEXANDER, F.D. J. clin. Endocr. £8 (1968) 575. ) SHIMMINS(5 , J.G., ALEXANDER, ¥.D. This publication. (6) INTERNATIONAL ATOMIC ENERGY AGENCY, Brit. J. Radiol. _3Jj (1962) 205. ) ROBERTSON(7 , J.W.K., SHIMMINS HORTON, ,J. , P.W., LAZARUS, J.H., ALEXANDER, ¥.D. In "Dynamic Studies with Radioisotopes in Medicine", International Atomic Energy Agency, Vienna (1971) P. 179. ) WAYNE(8 , E.J., KOUTRAS, D./U, ALEXANDER, ¥.D. Clinical Aspectf o s Iodine Metabolism, Blackwell Scientific Publications, Oxford (1964) ) ROBERTSON(9 , J.¥.K. Multiple radioisotope tracer techniquee th n si stud f iodido y e transport mechanism mann i s , Ph.D. Thesi, s!_ Universit Glasgof o y w (1970) p.120. 82 PERTECHNETATE IODIDE Thyroid kTB Thyroid k Subject Sex Diagnosis Thyroid Status Unidirectional Unidirectional TB Clearance (min"1) Clearance (mirT (ml/mi n) (ml/mi n ) AL F Depression Euthyroid 38 0.117 50 0.071 CR F Cerebrovascular Euthyroid 25.5 0.152 44 0.048 Accident KM IY1 Hypertension Euthyroid 41 0.041 119 0.079 LO F Respiratory Infection Euthyroid 64 0.096 100 0.123 RUN F Chronic Bronchitis Euthyroid 10.6 0.071 24.5 0.037 SIYI F Diarrhoea Euthyroid 15.3 0.031 51.0 0.049 GL F lYlintral Stenosis Euthyroid 27.0 0.043 56 0.066 PH F Asthma Euthyroid 22.8 0.035 82 0.050 FE F Epilepsy Euthyroid 8.6 0.024 28.8 0.028 CO RUT F Asthma Euthyroid 68.5 0.055 92.0 0.038 Mean 32.1 0.067 64.7 0.059 SEIY1. 6.6 0.013 10.0 0.008 30 IY1 Thyrotoxicosis Thyrotoxic 329 0.042 296 0.031 mu F Thyrotosicosis Thyrotoxic 70.5 0.165 164 0.115 IY1CA F Thyrotoxicosis Thyrotoxic 66.0 0.067 190 0.069 NE F Thyrotoxicosis Thyrotoxic 171.0 0.031 221 0.035 lYIean 159 0.076 217.8 0.063 SEM. 61.6 0.030 28.6 0.019 Table 1 The results of the studies inhere carbimazole was given to block the organification of iodide. Unidirectional Exit Rate Binding Thyroid Clearancek C , Subject Sex Rate, k Status lu —1 -1 ml min min min""1 U.C. m Thyrotoxic 676.7 0.016 0.184 E.H. F Thyrotoxic 69.2 0.014 0.049 m. .H F Thyrotoxic 382.6 0.015 0.118 E. L. F Thyrotoxic 200.1 0.010 0.170 IYI.L. F Thyrotoxic 100.8 0.017 0.071 I.fflcA. F Thyrotoxic 171.2 0.031 0.080 D.iïlcA. F Thyrotoxic 205.7 0.024 0.067 A.iïlcK. F Thyrotoxic 319.8 0.027 0.170 IKI.iïlcL. F Thyrotoxic 109.4 0.010 0.072 D.IYlcIïl. F Thyrotoxic 95.1 0.038 0.135 V.IYIoN. F Thyrotoxic 83.8 0.016 0.134 S.lïlcP. F Thyrotoxic 112.5 0.045 0.120 S. P. F Thyrotoxic 107.4 0.016 0.090 IYI.R. F Thyrotoxic 196.7 0.023 0.074 S.S. F Thyrotoxic 109.7 0.030 0.110 Mean Thyrotoxic 196.0 0.022 0.110 (S.E.IK1.) (41.4) (0.003) (0.011) A.B. F Euthyroid 41.4 0.009 0.042 C.H. m Euthyroid 45.2 0.046 0.050 U.K. m Euthyroid 27.9 0.016 0.092 E.IYlcF. F Euthyroid 30.1 0.048 0.104 E.IYlcI. F Euthyroid 30.9 0.038 0.053 E.lïlcP. F Euthyroid 30.1 0.017 0.007 A.UJ. m Euthyroid 52.3 0.038 0.115 Mean Euthyroid 36.8 0.030 0.066 (S.E.IÏ1.) (3.6) (0.006) (0.015) TABLE 2 ANALYSIS OF TRAPPING AND BINDING FUNCTIONS IN 15 THYROTOXIC AND 7 EUTHYROID SUBJECTS (Results of Binding Studies) 84 Subject S.M. THYROID UPTAKE PERCHLORATE l%Dose) DISCHARGE I Uptak"' • e x 99m Tc 24 40 56 72 88 TIME after ISOTOPE ADMINISTRATION (min) Fig. 1 (a) Thyroidal I and Tc for subject SIY1 is seen to be discharge perchloraty b d 0 minute5 e s after isotope administration. The action of the perchlorate is seen to take place almost immediately after administration. 85 Subject S.M. SERUM ACTIVITY (% Dose/ml) •015-1 •013- • 131 •011- •009- •007- l l l •00l 5 l i 0 16 32 48 TIME after ISOTOPE ADMINISTRATION(min) Fiq. 1 (b) The serum activities of I and Tc are seen prior to perchlorate discharge. In every case, the Tc serum activity is 131 higher than the correspondin I activityg . 86 13.1 UNIDIRECTIONAL CLEARANCE ml/min 400-1 300- 200- 100- 1 100 200 300 400 »""Te UNIDECTIONAL CLEARANCE (ml/min) 131. e best lineTh fi t _Fiq s2 correlatin. g unidirectional clearancf eo d unidirectionaan l clearanc e shown ar f e ~"unidirectionaeo Th c "T . 99ml. , subjecte excepis clearancon I n ti , f alwayeo s13 greate1 r than 99m, the unidirectional clearance of Tc. 87 BOUND POOL Kb THYROID GLAND IODIDE POOL h IB BLOOD opee Th nFig thre3 « e compartment mode iodidf lo e trappind an g binding. THYROID UPTAK f IODINE-13Eo 1 vs.TIME Thyroid Uptake SUBJECT A.McK. (X Dos«) 90- *-.*-*-' 70 TOTAl LEAST-SQUARES CURVE: 50- Unidirectional Clearance - 319-8 ml.mln"1 Exit Rate Constant - 0-027 mln~ 1 Binding Rate Constan 0-17" 0t cnln" 30- 1 10- UNBOUND I I I I 0 20 40 60 80 IOO I20 HO I60 Time (min) Fig. 4 The results of the kinetic analysis (binding study) for subject A.IKlcK. (hyperthyroid). 88 Summary An open three compartment model of the human thyroid has been used. This model contains three kinetic constants unidirectionae th ; l clearance; kTD the fractional loss rate of iodide from the gland; and kD the U D l fractional organic binding rate of iodide in the gland. The unidirectional clearance (c) and k haue been evaluated for iodide and pertechnetate when IT Do the organic binding of thy'roidal iodide urns blocked by carbimazole unidirectionae Th . 0) (i.e= n k l. clearanc n havk d e an als(c) n T o,k D l D D been evaluated for iodide for subjects not given carbimazole. A comparison of the results of these tuio studies suggest that carbimazole may affect the rat f thyroidao e l iodide trapping. 89 QUANTITATIVE SCINTIGRAPH E STUDTE N YYI OF EARLY THYROID UPTAKE B. Bok Departemen s Radiationde t s Institut Gustave-Roussy Villejuif, Prance ABSTRACT This paper first reviews the general problems inherent in early thyroid radionuclide uptake measurements, with particular reference to clinical requirements, choice of radionuclide, choice of measuring device and processing of the data obtained. It then describe author'e th s s personal experience carryinn si g out measurements of 99 Tc m uptake by means of a technique involving off-line computer analysis of digital data from a single-detector scanner recorded on magnetic tape. The computer program used allows correction of the data for radioactive decay, subtraction of background, smoothing, computation of the total number of counts recorded within a given contour of constant percentage count- g ratcomputatiod in an e aree th a f encloso n e within suc contourha . The results of detailed physical studies aimed at establishing the technique usea fir n mo d basi e give ar sn detaili n , particular attention being given to the problems arising from variations in the e leveth f extrathyroida e thyroio ln dept i th d f o han d l radioactivity, Illustrative results obtaine a singl n i d e hyperthyroid patiene ar t also presented and the clinical value of the technique discussed. IBIBQEffiTIQJ Thyroid uptake measurement using I is a suitable and accurate enough techniqu usuar fo e l clinical purposes. However, the interest of early uptake measurements is now emphasized n thiI . s case correctioe ,th n necmethode th k r fo s extrathyroidal activit satisfactort ye y t (ETAno e )ar y (l), (2), (5)d an . (3)) ,(4 91 Furthermore, for these early uptake measurements, the use of I instead of I provides a lower radiation dose to the subject, but needs heavy and expensive devices. Moreover, it does not permit scintigraphy, a.nd needs double-tracer methods (6). Then the use of 99T o m for both scintigraphic and dynamic studies seems to be of great interest (?)» (8)> provided that e horrconosynthesith t onle uptakno th yd an e considereds i s . correctioA AnET n formul proposes wa a d r iodidan fo d) (9 e pertechnetate (lO) t scatterin,bu importants i g givet i ; s only mean values. A "wash out1' method by thiocyanate injection was also described (7) differenr ,o t thigh activity correction formulas. But these correction method e unsatisfactoryar s . Furthermore the low energy of the Tcm gamma rays (140 keV) increases the rôle of thyroid depth and thickness. For these reasons, the usual methods with a non-imaging fixed detecto e inadequaterar d scintigraphi,an c methods have been described by several authors. First e shal,w l discuss general problem d givr personaan sou e l results in a second part. GENERAL PROBLEMS D PHYSIOLOGICAAN M AI - 1 L PROBLEMS e generaf thesTh o m eai l method measuremene th s i s f o t thyroid uptak givea t ea n time which should provide clinical infor- mations. Tim- Aduratiod ean n Iodide uptake occurs early and a 20 minutes measure- men mostls i t ) (10y(8 use) (7 d(11) . Variations of cervical activity are quick in the first minutes (8) measuremene .Th t duration must the shore nb t enougo s h that the required value remains a constant. For moving systems scannee ,th r speed varies between 30 - 50 cm/tain (S) and 1 ra/min with a 0,85 cm line spacing (9). 92 E - Signif ication These measurement nade sar e under different circumstance: s 1 - The purpose can be to perform comparative t'easure- ments on the same patient (stimulation or suppression tests) (12) (13) (U). The result by itself is not of great interest ; it needs to be compared with the others. Reproductibility is then the most important require- ment and relatively great méthodologie errors can be accepted. For instance, when the uptake is overestimated because one has omitted the depth correction resule a suppressibilit,th f o t y test will regain correct. 2 - On the contrary, the purpose can be to confère a dia- gnostic value to one measurement. Under these conditions, the metho- dological care and exactness will play a prominent part. e santh e s Ii whet n these result e use establiso sar t d h clearances or other functional parameters. IRADIOISOTOPEI- S 131 Iodine was first used (10) (18). Its medium energy (364 keV) gamma Rays provid advantage deptw th elo ha attef o e - nuation (18) (19). m Teelmetiu 9 9 n>orw no es i mwidel y used s n spitit .I f o e lower energy, it provides a considerable radiobiological advantage since the average dose delivered to the thyroid is only 0,1 rad for 1 m Ci injected (20). II DETECTOI- R DEVICE Sensitivit- A y Wit commonle hth y used activitie irC.)1 ( s , thers i e always enough sensitivity to avoid statistical inaccurracies unless the uptake is very low. E - Spectrometry Its importance was shown by J^HNSTOK and BRILL (21) varaibilit e dwelo th wh n COMPTON/photopeae to th f yo k ratie with depth. Kost workers use a narrow pulse-height window, centered on the photopeak (120-160 keV (10) ) or do not specify their measure- ment conditions. It is however an important point : the measurements should be made always under the same conditions and a "drift" should be avoided. But a wider-pulse-height window might be better, since the purpose is not to obtain a fine resolution scan image but a dotse th metho.f o r countinm dfo su e th g 93 n thinca ke thaOn depte th t h attenuatior pa e b n nca tially reduced this way, modifyin COMPTON/peae th g k ratio. However threshole ,th d must remain high enoug avoio t hleae th dd X rays. As far as we know, only general considerations have been mad n thieo s probier .appliet e (21 ye th wer t t o )bu t deno specific proble f thyroimo d uptake. Sensitivity variations versus depth "The response to a large thin plane source, having cons- tant activit unir ype t area, doe distance t depensth no n o d e fror. the sourc f atteittei a tio neglectes ni d certaidan n approximations are made (19) (22). " Furthermore, HARRIS says (23) that "the quantative value of counts fro scannerma , movin stationaryr o g reinforces ,i y db the fact that, as long as the scan completely covers the target, the total counts recorde indépendane ar d sourcf o t e distanc. " e However, that is only true when the "sunned" area (i.e the aera inside of which the dots are counted) is wide and more especially when the depth increases. That would lead to consider wido to e a arecountinr fo a thyroie whole th th gf eo d activity and so, to increase the part of the E.T.A. (cf infra). Furthermore, the attenuation in water of the Technetium gamma rays neglectede shoulb t no d , althoug dependt i h s upoe nth detectioe source th th sizd f ean o n conditions (21). Several ways were then chose: d correctioa e us ) 1-(7 nANDRO. tablal t Se e versus thickness and depth of the thyroid gland as they are estimated on clinical and scintigraphic data. ) conside(8 ATKIN. - al 2 r t Se tate errore th th h n si determination of these correction factors are so important that they hav actuao en l interest same th e n wayI . ,) HIL(9 Dl a ITC t He discuss this problem in the use of 131 I without giving any answer bulaten ti r paper discusst no the o yd s this point when applying the same method to Technetium uptake (10) (14). However- 3 , this fac importans i t pointes y ta b t ou d ARIMIZU et al. (19) and WILLIAMS and De GAPRETA (11) (24), who emphasize the need of a depth- indépendance response of the detector. This is obtained by ARIMIZU (19) by perfoming two scans pronn i d supinean e position d directl,an WILLIAMy yb S wit hduaa l detector scanner thes i nt . I necessar tako yt e into accoune th t nec conveniena dote k y th thicknessb p u d tad swayo t (11 .d )an Arithmetic and geometric means are discussed. 4 - However, we think that this problem is less important in quantitative scanning of the thyroid becauseit is a thin and superficial organ and there are two reasons of this : 94 lowee th pare rf th to detecto - a r (which "sees" the nape of the neck) is rainor : its contribution is also less important than a phanton study could make believe. Under these conditions indeed, the effect of bone attenuation is neglected ; now the bone thickness and distance from the thyroid gland are quite variable according to the patient, Furthermore- b thyroie ,th usualls i d y thid nan superficial dept e goiterg excepth bi hr d variationtfo san n si efficiency remains within acceptable limits. But this point must be experimentally teste every b d y laborator avoio t y greaa d t inaccurac uptake th n eyi determination. IDAT- V A OUTPU HANDLIND TAM G Dat- A a output The simplest way is to count directly the dots on the scan image r thi.Fo s purpose higa t easiee s hdo i us t ,o i t r factor and a wide space lining. computea e n bettefacts I i us datr t o ,i fo rt r a pro- cessing (18) . B - Choice of the area limits The methods using directly the dot scintiscan with di- rect manual counting allow only very simple calculations derived from gross estimated area simplf so e geometric shape. Thes- eme thods are inaccurate, the more so as the pertechnetate E.T.A. is heterogenous. The use of a computerized method should provide a better answe thio t r s problem. However, chose) TAUX 8 (1 Ed "the lowest counting level which most closely corresponded to the outlinthyroie th f eo d gland (above background threshold)" but without definin exace th g t significatio f "mosno t closely". Indeed, "the presenc higa f heo leve f radioactivitlo y in neighbouring organs may, however, seriously interfere with the measuremen radioactivitf to bodn i y y organ quantativy sb e scintigraphy." (25) have W e observed thaapparene th t t glane limitth df so can be widely modified by the level of E.T.A., and this can be the source of erroneous results when it is not corrected. CalibrationC- - Calibration problem greaa r tsfo part depends upoe nth variations of efficiency with depth. If efficiency is depth indépendant (or little dependant) the phanto e criticashapt th no f es o mi l (11) (18t )no (bus i tt i always so). 95 procedureo Tw then uaee ca scalibratior nb dfo : n I/ with each measurement n aliquo,a e injecte th f to d solution is introduced in a more or less "anatomic-like" phantom and the measures are p.ade in the same way on a "phantom-neck" and patiente onth ) (18)(9 . . 21 using a thyroid "anatomic-like" phantom, a calibration factor is carefully determined between this phantom and a syringe. This calibration facto thes ri n use calculato t d e thyroith e d counts/syringe ration for each patient (11). We prefer this se- cond way. PERSONAL RESULTS MATERIAL METHODD SAN S - Scanne1t pu d dat t ran aou We use conventionnaa d l movin heae on gd scanner (MECASERTO M.0. wit ) inche3 4L ha s diameter1 6 crysta a d lan honeycone holes lead colliraator e scannin.Th 5 ens/secg 2, spee s ,dwa with a 2,5 mm line spacing. pulse Th e height analyse rbetweet windose 5 s n10 wwa and 175 keV. Summation of pulses was performed each 1,25 mm and re- corde Kenneda n do y incremental mapnetic tape together with timer signals. 2 - Phantoms and calibration We use "antomic-liken a d " moulded thyroid plexiglass phantom filled with water, the inner volume of which was 51 ml and surface th e projectio meae nTh n2,54» thicknes m 0ra . thes si cm n2 This thyroid phanto places plastia mwa n i d c box, 30 x 11 x 9, cm ; filled with 3 liters of water ; and depth could be adjusted. For calibration, a 2 ml syringe was used, filled with pertechnetata e solution, injectede readb o t y . This syrings ewa place hola n ei d situate plexiglasa deem c n i pd3 s cubic block of 12 x 12 x 12 cm. Two scans were performed, before and after the injection. 96 3 - Computer Processing and date output. Magnetic tapes are fed into a high speed digital computer (UNIVAC 1107) to reconstitute the data matrix, each line being 2,5 mm and each column 1,25 mm. prograe Th m allows backgroun decad dan y corrections (fo scaa r fror nscae o another)mon o n t , smoothing followinga chosen method, cells summing when necessary. Moreover, what is essential for our purpose, it can give the total number of courts and for each needed level (in percentage) the surface inside of this level and the corresponding number of counts. We have chosen each 5 % level from 0 to 50 %. It is also possible to use an automatic-plotter to ob- tai colouna r scanimage, each colour correspondin zona o et g betwee o isopercentagntw e limits. RESULTS 1 - Choice of the colliciator-skin distance ( h cm) (Study on a line source) Technetium A lin 9 9 e m sourc places m e"eewa c 3 dp in plexiglass (mean depth of the thyroid gland) and spread func- tions were reformed for several "collimator-skin" distances. Results are given in fig. 1 a, b, c. The most important are: Unde- 1 r these conditions, focusin e collimatoth f o g r is obtained for h - 8 cir, i.e. collimator focus is at h •*• d = 11 cm. 2 - At h => 8 cm, both sensitivity and resolution are , cm 5 optimal9, untim c = 6 lh frot = ,bu mh sensitivity remains over 90 % of this maximum. We have then made the following measurements (role of decrease Th . cm e 6 wit = hh deptr fo hd an m c depth 8 = )h bot r hfo was less important for h :*= 6 cm than for h = 8 cm (an explanation of this is that the focusing effect provides some compensation depte foth r h effect)resultl Al . givefige s( .b) b wil2 .w n lno fo collimator-skira . n cm distanc6 = h : e 2 - Variations with depth (d cm). a) line source Spread functions were obtaine differenr fo d t depthn si plexiglass. 97 Results are given in fig. 2 a, b, c. The important result is that efficiency remains over 90 % depthm froc 5 unti m0, 0 decreaset I .4. l s very quickl, y or after 0 4. to 70 % at 5 cm and 58 % at 6 cm. This means that efficiency does not change too much and provides a good technique for uptake evaluation, with an inaccuracy due to variations in depth nor exceeding 10 to 15 % on the result, unles measuremene sth largmada s ti n eo e goiter. b) Thyroid-phantom source Quantitative scans were performed at different thyroid depths in water. Results are summarized in table 1 and II (three percentages only are showed here). Main results are : 1° - The shape and size of the chosen isopercentage sur- faces (S , i.e. surface inside of which the counting rate is over ? 12 % of tn1 e maximum count-rate over the thyroid gland S 31.63 and 45.33S undependane )ar depthn to show.e b Thi tabln n no sca I e and directly on the scans which are not represented here because they are coloured documents. e isopercentagTh - ° 2 e which best fitactuae sth l thyroid surfac . Thi % neas ei s0 r 3 poin t wil developee lb d later. decrease Th - countf ° eo 3 s with critica t deptno s i h l between 0,5 and 2.0 cm, since the total number of counts remains depthm c % (tablove0 fine .W 7 3. 8 r d t ea II)% fall5 t .7 I t sa agai stude resule th nth yf to wit hlina e sourc thi: e s factor remains acceptable, except for the large goiters (our phantom is bigger tha nnormaa l thyroid gland s liki moderata et ,i e goiter). 4° - Whatever isopercentage taken, this decrease is nearly the same. We have shown in fig. 3 that obtained for the S 31 surface. 98 Consequence- C calibratior fo s n TABLE I - Values of the surfaces S - (corresponding to the inner side of an iscpercentage line i %) for different depths of the thyroid phantom. nini2 depth(cm% ) 2 1 S S 31,6% S 45,3% 0 3,694 2,675 1,962 0,5 3,656 2,6öo 1,850 1 3,650 2,675 2,112 1,5 3,625 2,662 2,031 2 3,637 2,581 1,925 2,5 3,650 2,706 2,037 3 3,525 2,594 1,894 » 99 TABLE II - Number of counts tatalized in the different S^ surfa- ces at different depths (the second number in a division depthm c 5 belo)0, firse r wth fo normalizes i t% 0 10 t a d depth insidf eo % 2 1 S S 31.6 % S 45.3 % 0 16,774 14,862 12,379 (108) (109) ("D 0,5 5 1548 , 13,571 11,076 (100) (100) (100) 1.0 15,013 13,423 11,710 (97) (99) : (105) 1,5 14,069 12,528 10,628 (91) (92) (96) 2.0 13,535 11,855 9,904 (87.4) (87.5) (89.5) 2,5 12,389 11,101 9,398 (80.0) (81.8) (84) 3.0 11,860 10,541 8; 702 (76.6) (78) (78.5) Depth play determinatioe th parsa n i t calibraa f no - tion factor. Thimuse estimatee on stb fixea t a dd depthr ,fo instanc m beloc watee 1 eth w r surfac d wil ean e applie lb d to any patient with an error which cannot be precisely estimated, but which will stay lower to 10 % , in most cases. The choice of isopercentage can be made arbitrarily since the S. surfaces widths do not change with depth. syringee Foth r retainee ,w larga d e surface (S]0) to take into accouninformatione th l tal s coming fro e sourcenth . For the thyroid phantom however, we have taken the iso- percentage which fits besactuae th t l thyroid surface. This point has no importance when no extra thyroïdal activity is present, but becomes useful in the opposite case. We found a calibration facto syringr (o r e factor S.F.) Q.96 100 Variation- 3 s with extrathyroïdal activity (E.T.A.) The thyroid phantom was filled with 100 microcuries d placea tandeea an n er ki p c 1 T dfille 9 9 witp u d h water whicn ,i h increasing amounts of pertechnetate were added. Its thickness was 9,2 cm. Their respective .positions are shown in fig. 4. Scans were performed for several E.T.A. and results are given in tables III and IV. Several points are of interest : eacn i h) a column (i.e eacr .fo h isopercentage th f o e maximum activity) both activity (A".) and surface (S.) (correspondin innee th risopere o t gth sid f o e- centage ) increaslin% i e e with E.T.A.Thi s eviswa - . sincA denr efo t total activity increasest no t ,bu t surprisingno thougS s i r t fo i h . appeart bI . n tablo s I thae isopercentagII e th t e line that best fitactuae th s l phantom surface projec- tion (i.e. 2,540 mm ) increases with E.T.A. between firse th tr linfo % % e5 4 0 (E.T.A3 ; d ) 20 5an .= for E.T.A. = 23.10~ (fraction of thyroid activity / mm ) . This point is not taken into account by most authors but seems for us of great importance. c) For each line on table III and IV (i.e. for each E.T.A. level possibls i t )i determino t e e th e best fitting percentage (F.P.) and the corres- ponding numbe countf ro s (F.A) insid f thio e s "fit-percentage". This interpolatio made b en ca n by simple calculation (arithmetic interpolation or graphically (as shown in fig 5.) or co^pute^- calculated. establisn Thenca e ,w ha tabl F.Pf o eF.Ad .an . versus E.T.A. {tabl plod grape an th t F.Pf ) ho eV . versus E.T.A. (fi) 6 g Thuseass i correco t yt , i r extrfo t a thyroïdal activity using a simple calculation method: F.A. is equal to the sum of counts due to both intra thyroïdal (I.T.A.) and extra thyroïdal activities in the actual thyroid phantom surface (2,540 ram^j F.A. Thu I.T.A: s . (counts) =-———————————-—=———-————— I + 2,540 x -^——E 101 CN ü •r) ro u o) O CO vO r--. co 0 o 00 o» co ~ O co CN ^ ^ ^ * ^ K "~ * • • ' 1 I CN 6-8 00 »H O 00 r-» -a- H t« 00 CO er» vO 4J 0 -o- OÏ CN 0 m O \O a c 00 O 1—1 CM co CO 4J 4) •s Ü *T3 **^ ÎU O1 CO CM O CN m m CJ n3 0 O 0 m r- CN cd >» Cu co -•3" m in VO (^ r _ j 4-1 V CO »H J-i ^ C-? CN CMN CN CN CM m eu > <ü ' • 4-1 U -H 0 rt CM ~* CN VO 4> 4) 1-, co m 0 00 Ö ^ l Oi- «n S r-. 00 r— ) ro 'S, y— \ CN H Ct) 4-1 CM CN CM1 (!) -Ö CN CM co" ro* ^ CX>H O e-« O O 4J to CO J-J 4) •H !>, 60 00 r-, CM •o- m n) co 3 O m 4-1 0 O CM CM m fN CO n ^ V O J 4 u) V CO 0 (^ CO CO l P l p »> M Cl -H tQ CO 4) O, «J M O n co vO O 4-> O •i-t — ~ *— » vO <4-l O m CM OO 4-t --' r-i CM 102 ——. ————— | ,_, m f-1 00 o fO CO in CO CM vO OQ r--. 0 in 00 n f) ^\ ^ vo ^ CM s ^ *. V V ^ V ~* vT m in in in VO on o *—* in vC 0\ in ~* tri o- 0 oo r-T r-. vo OO in oo •V «» 4v ^ V t* ** m in m m vO vo 0. CM co o T 0 'vO o & n -* m in 3 in vo vov o ^ i r-i 7— Ï r> 0 CM o CM CO in in -cf ro CO OO r-l G 00 •N m vo VO VO r-, CO r—l r-i m tn o in CM VO VD o £ vo CO O fO O VO CM •s s •s VO VO r-. r oo ^ "* CO -* ! en •al ro o in f) r—l o CM CM o IS o in ft CM i ro MD r-, r-. 00 CO of t« VO r> O m G CO co m ^ o ro O CO CM co »i VO CO oo tr, /— ^ •^ ^ r-1 sT 05 CO CO t--. r-t O vt OJ vO @ •o- 00 m O m +J m •O- vo o en in CM G N R oo" 00 CO o ro^ •vr? O n •" CM 3 O P. 0 co in en O OO r-. V] 0 CO m % r—1 m m • H •-r ro ^~V — «v ^ ^^ pN, CO OV o CM Vo VO r-f I—I r- CM M CO 1^1 O vo vo o (2 CO m vO i CO n O"» C r> C(N en"" *v V •V N *. r—i r-> n r—i CM 4) O CO CM CM 0 at CO O OO CO m H tEjt! § CO vo n N CO f- r CO oo M ^ r—: ip r—* CM ^ •> CO -a- 00 in H on -a- c^i CO O ib. «^ •k ^. s W o 0^ CM in — I ( CÎ i 103 Results of this calculation are shown on table V. Then thyroid uptake is immediately given using the calibra 4 tion factoshows a . par n c ni S r 2 t Determinatio- 4 E.T.Af no . Assumptions- a . calculationl al r Sfa o s were performed with known value thyroir sfo d siz extrd ean a thyroïdal activities. They were then only verifications upo validite usee nth th d f processo y . Since we did not repeat these experiments with other size thyroid phantom muse ,w t then make some assumptions to answer the actual question, i.e. determine E.T.A. , thyroid sizd thean e n I.T.A uptaked .an . The most important is that the relationship between the fit percentage P.P. and E.T.A. remains the same as given in . 6 fig. Once this point is assumed, it becomes necessary to find a way to calculate E.T.A. fron the processed data of a scan (i.e. S and A). b- E.T.A. Determination providn ca Tabl I relationshiea II e p between E.T.A. values and data extracted from the S„ _ . _ matrix. We are now trying such computer calculations, ancl two'ways are possible : a lin e e us regressio n ca e W 1- °n methoo t d determin formulaea fore whicf ,th o m h bein: g i S ^ E.T.Aa Z .= Two problems remain unclea: r - Are the low values cf £ (5 and perhaps 10) useful as the corresponding surface becomes too large for high values of E.T.A. (extra thyroïdal activity is not indeed an infi- nite extended source, according to the actual size of the neck) ? Inormalizatiosa n factor necessaryo s f i d ,an bese th answeo Ther? t n s i whics i ee r hon withou t further expe- riments with other-sized thyroid phantom. s curvee shape th Th versuf S so e- ° s11 iso- percentag I e(on f these o same r shows th i efo e t nno figs i .) 5 the different E.T.A. values. This point needs further computer studies grosa t ,sbu graphic stud alreadn ca y performede yb . 104 An eye study of the S/isopercentape curves family (as this shown fig. 5) shows two points : - an inflexion point is noted for the low percen- tapes, but only for the high E.T.A. curves ; e limiteth thao t de t e th sizcoul du f eo e db E.T.A. containing tank. - a slope breaking can be seen on all the curves and this breaking off point is translated to higher percentages when E.T.A. increases. Gross determination of the breaking off point absciss (B) is shown on fig. 5. Such determi- nation for the whole curves family allows to plot a curve ofB versus E.T.A. (fig 7). Ill - Whatever is the relationship established between the S matrix and E.T.A., it oust be assumed that it remains true for any actual patient's thyroid gland. CLINICA- 5 L APPLICATION (Exemple) Results obtained by a patient (who was hyperthyroïd) are . curveA plottee d ar san . S d e (figth show d . n tablan 8) .no , eVI B is readed out on this curver (9) and this value is reported on fig. 7., that gives E.T.A. value (2.5 x 10~5). Then F,P extracte.s i d from fig 6 (30.8. . 8 reported )g an fi n o d deperminatee Sar o d F.S. (Fit surfac i.e; e . actual surface) (2,220 ma2) and F.A. (9,200 counts). After that, I.T.A. is calculated according to the for- mula given before (3 C) : F.A. T T A = F.S+ 1 x E.T.A. . REMARK 7.2 The correcting factor -——- is not USed here because 9.2 there is in the thyroid a Vascular part without any significance of uptake, because the thyroid thickness is unknown, and because it lies on the thickest part of the neck. 105 Finally, uptak gives : ei y nb Uptake I.T.A. x calibration syringe counts factor x 100 % 2 Ther2 resule = = eth 6 8>78 9 s i tx ° 38,600 E.T.A. F.F. F.A I.T.A. 0 28.75 6,390 6,390 0,68 29.2 6,800 6,700 1.87 30.5 6,980 6,720 2.44 31. 5 7,150 6,800 5.38 33 7,400 6,680 7,35 34.7 7,600 6,630 11.3 36.5 8,150 6,660 23 45 9,577 6,600 TABLE V - For several values of E.T.A., the results of F.F. and F.A are given as obtained by plotting the curves as .shown in fig. 5. (Phantom studies) F.F. tseans the fit percentage F.Atotae th .l numbe innecounte f ro th rn si sid e of this fit percentage I.T.A.mean actuae sth l numbe intro f countt ro e asdu thyroïdal activities. Whe othen na mord an re accurate point wil reliable lb n i e the determination of F.T.A., the following will remain unchan- ged (but shall be computerized too). 106 DISCUSSION - Phanto1 m The plexiglass wall of the phantom, 1.5 ma. thick, modifie e spatiath s l distributio isopercentage th f no e surfaces. This seems not to be of great importance. 2 - Depth We have seeimportane th n t part playe y thib d s facto: r e heaon witd r collimatcrhou accurace ,th y limit cannot fall lower than 10 % (on the result). Limit3- s The most important fact we noticed is that the apparent size of the gland (as determined for instance by the 40 % isopercentage) increases together with extra thyroïdal activity. Our method permits to determine not only the uptake, but alsactuae th o le thyrbi< th siz f eo 2 gland. This point could be of great interest, for instance in the determination of the therapeutic activity to be given for a radioiodine treatment. E.T.A- 4 . determination mose th Thit s criticabli s e poin s showa t n previously. However, it seems to be preferable to any method using; geome- tric area belo thyroie wth d glan r correctiofo d n factor, which neglects both E.T.A. and I.T.A. heterogeneities. Clinica- 5 l interest This computer-assisted method is sophisticated and expensive, and that is perhaps the major criticism which can be made. It is then justified only when it provides irreplacea- ble resultevaluatioe th e thyroin si th f no d function. This point needs further studies, but it is probably true certain circumstan- ces only. REFERENCES ) JOYET(1 Med. ,G . isotop. Grenzgeb .^ (1956 . (1 (2) MYANT, N.B., HONOUR, A.J., POCHIN, E.E. Clin. Sei. 8 (1949) 135- (3) GOOLDEN, A.W.G., MALLARD, J.R. Brit. J. Radiol. 31 (1958) 41. (4) BERSON, S.A., YALOW, R.S., SORRENTINO, J., ROSWIT, B. J. clin. Invest. _31 (1952) 141. ) KDUTRAS(5 , D.A., SFONTOUEIS Endocr. J . ,J . _3j> (1962) 135. 107 ) PARMENTIER(6 MONNIER, ,C. , J.P. SAINT-MARTINe ,d méde Vi .. ,M 24 (1969) 3101. ) ANDROS(7 HARPER, ,G. , P.V., LATHROP. K.A., McCARDLE clin. J . .J . ,R Endocr (1965£ .2 ) 1067. (8) ATKINS, H. L., RICHARDS. P. J. nucl. Med. _9 (1968) 7. (9) HILDITCH, T.E., GILLESPIE, F.C., SHIMMINS, J., HARDEN, R. McG., ALEXANDER, ¥.D nucl. J . Med .(1967Q ) 810. (10) SHIMMINS, J., HILDITCH, T.E., HARDEN, R. McG., ALEXANDER, W. D. J. nucl. Med. 10 (196l) 483. (11) DE GARRETA, A.C., GLASS, H.I., GOOLDEN, A. W. G. Brit. J. Radiol. 41 (1968) 896. (12) ALEXANDER, W. D., HARDEN, R. McG., SHIMMINS, J., McLARTY, D., McGILL, P. Lancet ii. (1967) 68l. (13) ALEXANDER, ¥.D., HARDEN McG.. ,R , SHIMMINS McLARTY, ,J. , D. , McGILL, P. J. clin. Endocr. 27 (1967) 1682. (14) SHIMMINS ALEXANDER, ,J. , W.D., McLARTY ROBERTSON, ,D. , J.W, .K. SLOANE, D.J.P. J. nucl. Med. _12 (1971 ) 51. (15) SHIMMINS, J., JASANI, B., HILDITCH, T., HARDEN, R. McG., ALEXANDER, W. D. J. clin. Endocr. 28 (1968) 111. (16) ROBERTSON, J.W. K., SHIMMINS, J., HORTON, P.W., LAZARUS, J.H., ALEXANDER n "DynamiI . D . ,W c Studies with Radioisotopen i s Medicine", International Atomic Energy Agency, Vienna (1971 199. )P . (17) SHIMMINS HILDITCH, ,J. HARDEN, ,T. McG.. ,R , ALEXANDER, W.D. clin. J . Endocr (19688 .2 ) 545. (18) TAUXE, W.N nucl.Med. .J (19610 ._1 ) 258. (19) ARIMIZU, N., KA.KEHI, H. In "Medical Radioisotope Scintigraphy" I, International Atomic Energy Agency, Vienna (1969) p. 653. (20) SMITH, E.M., J. nucl. Med. 6. (1965) 231. (21) JOHNSTON BRILL, E. . ,R , A.B "Medican .I l Radioisotope Scintigraphy" I^j International Atomic Ener.gy Agency, Vienna (1969) p. 6. (22) BROWNELL, G.L. In "Medical Radioisotope Scanning" 3_, International Atomic Energy Agency, Vienna (1964. 3 . )p (23) HARRIS, C.C Procn .I . Symposiu Computern o m Scanningd san Nucl. c .So . Med. Yorw ,Ne k (1967. )50 (24) WILLIAMS, E.D., GLASS, H.I., ARNOT, R.N. GARRETAE ,D , A.Cn .I "Medical Radioisotope Scintigraphy*' 1^, International Atomic Energy Agency, Vienna (1969 665. )p . (25) INTERNATIONAL ATOMIC ENERGY AGENCY, Int appl. .J . Radiât2 ._2 (1971) 385. (26) BOK, B., Di PAOLA, H. , BAZIN, M., TUBIANA, M. (in the press). 108 9. CM. 8. CM. 7. CM. 10. CM. Lin§ a Fige I .sprea d functio . nDept f m sourcho c 3 d= e Collimato - skir n distanc evaryinm incrementh c I t ga s- 109 max. 90. efficiency 60. 30. 0. . -l .i l l l l M l p M I I I I I 0. 5. depth (cm) Fig. 1 b - Efficiency versus collimator - skin distance h (cm) (depth » 3 cm) (line source) -—K Index 0 » resolution 0. 5, (nun) depth (cm) Resolutio- c Fig1 , n index (widthcurve th halt maximus ea f , o it f m amplitude) versus h 110 2 . 5 CM . 0.5CM 6, CM. 6 , 5 CM . . 7. CM. «•• - 111 99. 89, 79, U •r-l M-l 4-4 W 63, 59. 6.5 Depth (cm) Fig. 2 b - Efficiency versus dep-h d (0,5 cm increments) - dottee th d e solid an Th lin m dc e lin 6 fro fros = i e mh mh = 8 cm 112 \\.7 0) T3 fi oC O ta 0) 10.7 9.7 8.7 Depth (cm) Figc 2 . Resolutior) . n indee 6 x= versuh ( d s 113 80 » i I 2 3 cm depth Fig 3 : Variation of number of dots inside of S, versus thyroid phan i depth 114 ! il. I..1 I HI I h .1. ! .11 J. \ U M I l I I l Il ! . I . I I ! I I I 1 J I I I HIM. U I J I". 1.1 1.1. Jl. III. I I Ill I illl i J ] l l MM::h l mi l i ; i IP vi, I I ! I ! i i ! Ill '. ..".I'lilM'..'!.!,'.'! : FiUntreate 4 g d scan (showin e thyroie limitth th g f o sd phantom and of the surrounding water-filled box). 115 Activity (counts) Surface (mm ) 15,000 inflexion 50% 2 —5 fig.5 Variations of S,^ (mm ) and A. (counts) versus I (E.T.A.= 7.35 X 10 ) Determination of P.P. and corresponding values of F.S.(=actual surface )and F.A, Determination of B (see text ) 116 fig.6 percentagt Variatiofi e th f eno (P.P.) versus extrathyroïdal activity(E.T.A.) 117 20% 10% 0% 0 5 10 15 0 2 E.T.A. fig.7 Variation of B (absciss of the slope breaking off point) versus E.T.A. Each point is obtained as shown on fig.5 10.00Q ° / Activity (counts) ••o Surface (mm ) 10,000 /\ F n.<- 9 o 5.00TT- ——T" —r- ——T" 15% 20% % 2535 % . T* . F 2 30 40% 45% 50% A, 2°) FIG8 Variatio. (countss . G...A Mr d S^mf $ o nan ) ) m) ) versu % ( I s ) Grajtphica1° l determinatioB f o n ) Usin2° calculatee th g d valu P.Pf o e graphica., l determination of F,S. and F.A. see text 119 THE PERFORMANCE OF THE IAEA STANDARD COLLIMATOR FOR THYROID RADIOIODINE UPTAKE MEASUREMENTS WITH RADIONUCLIDES OTHER THAN . DaoRG . u Medical Applications Section Divisio f o nLif e Sciences International Atomic Energy Agency Vienna, Austria ABSTRACT The paper describes studieperformance th f o s standara f o e d collimator developed by the International Atomic Energy Agency for thyroid I uptake tests with other radionuclides used for thyroid . WitI e th h d uptakan I e tests , particulao n T i , , I r first thre f theso e e radionuclides, bot e sharpneshth cut e th - f so effectivenese th d an e sidf th e of f so shieldin g were better than with I, in accordance with predictions based on the energy of 132 their photon radiation. however, WitI h , which emit sy ray f so energyn i V 1.3o ut pMe 9, performanc grossle s founb ewa o t d y inadequate both as regards cut-off and side shielding, and a con- siderable increase in the thickness of the lead alloy would be necessar achievo t y esatisfactora y performance. INTRODUCTION Novemben I r I960 Internationae ,th l Atomic Energy Agency (IAEA) sought the advice of a group of experts on a project of assistance to its Member States in the calibration and standardization of thyroid radioiodine uptake measurement techniques. This group developed a set of recommendations which have since been published in a number of journals and in several languages (l), these recommendations applying primarily to 24-hour I uptake measurements. Three of them, relating to shieldin d collimatiogan e radiatioth f o n n detector, wers a e followst 3.2.1visuae Th .l workine fielth t a dg distance shoule b d preferabl d certainlan 2 1 y greate t no y n diametei rm c tha 5 n1 r 121 in adults and proportionally smaller in children. This field is defined as the region within which the counting rate from a poin t doeI t falsource no sl th cenr f "beloo ef pe o t 0 9 w value recorded at the centre of the field if the point source is moved at the working distance. 3.2.2. If the source is moved at the working distance "beyond the edge of the visual field, the counting rate should fall to 50 Per cent or less as the distance increases "by 20 per cent, and to 5 Per cent or less as this distance increases "by a further 20 per cent. 3.2.3. Wit furthea h r movemen poine th tf o tsourc e away from the axis at the working distance, the counting rate should fall rapidly and remain "below 1 per cent of the maximum value except e regioth n i n "behin e crystath d l whic s definehi a soli y "b dd angl exceedint no ecenr pe t 5 g2 (on e 7. Withi t) n this region, the counting rate should not exceed 15 per cent of the maximum value. Sinc collimatore th non f o e a then available commerciall thest me y e specifications, a standard collimator having the recommended characteristics was developed. This collimator, which is shown in Fig . 1, was like- wise intended primaril 24-hour fo yuptakI r e measurements wa d san designe havo t d ea fiel f vieo d w 13-n diametei 5m c r when workina use t a d g A det ?. cm 5 tanc2 f o e s "beeha n, I published. Since that time, radionuclides othe, I r notabl , tha, I To n y "l ~\o and I, have been increasingly employed in investigations of thyroid function coult I . predictee db d thae performancth t e standarth f o e d collimator woul perfectle db whic, I y hsatisfactor d an c T y , witI h emit photons with energies t thalowebu t, rI tha rayy ne f so thosth f o e 132 its performance would be inadequate with I which emits y rays with energies considerably higher than those of I. This paper describes studies undertaken with the object of confirming these predictions. METHODS The experimental arrangements were similar to those previously described (2). The scintillation probe used in conjunction with the 122 collimator incorporated a sodium iodide crystal 1 inch in diameter and was coupled to a sealer through a single-channel pulse-height analyzer set to operat a simpl s a e e discriminator. Measurements werr eai carrie n i t dou with point sources prepared by evaporation from solutions of the various i p "3 radionuclide n lighi s t Perspex holders. SincI (y-rae y energy 0.159 Me?) A T readilwat sno y available o (y-raS , y energy 0.160 MeV uses )placn wa i d e thif o s radionuclide r eacFo .h radionuclide discriminatoe ,th t se s rwa nea lowee rth rmaie limith n f photo-peao t pulse-heighe th n ki t spectrum, thus excluding the greater part of the Compton-scattered radiation from the measurements; the settings used are shown in Table I. TABLEI Discriminator Settings Used Energf o y predominant Discriminator Radionuclide setting X or y ray (MeV) (MeV) 125l 0.027 0.020 99mTc 0.14 0.10 4- T « oC 0.16 0.10 132, 0.78 0.60 RESULTS Visual field sho5 resulte d th w an studief visua4 e so » Pigsth 3 f l, so 2 . fiel f o d the collimatorI wit, "TchScI, l(fo) a antr ad working m 47 123 132 distance of 25 cm.125 In these studies the sources were moved along the arc radiun i circla m c f s o 5 centre2 emid-poine th e fron t th da tf to surfac e of the crystal housing. In each case the data are compared with those for previouslI y reported. 123 Side shielding 9 shoresulte d wth an similaf 8 o s Figs, 7 r, . 6 studie adequace th f o s y of side shielding with the same radionuclides, the sources "being moved around the probe-collimator syste from mid-poindistanca e c th t m0 e a m 4 th f o ef o t front surfaccrystae th f o el housing. Again eacn ,i h casdate e th eaar compared wit previouslI h thos r fo e y reported. DISCUSSION The results confir predictee th m d satisfactory performance th f o e standar whicf o sharpnese wit, I l th hh al d collimatod san c T r, witI h of the cut-off as the source is moved "beyond the edge of the visual field and the effectivenes e sidth ef so shieldin e "bettegar r than . witI Indeedh , it should he possible with all of these radionuclides, above all with 12'I5 , to reduce considerably the thickness of the lead alloy in all parts of the collimator and still satisfy the recommendations of the expert group. With 132I on the other hand, the performance of the collimator is grossly inadequate lowese Th . t counting rate recorde source th moves s i ea d d beyond the edge of the visual field amounts to 1.5 per cent of the value recorded in the fielde centrth f ,o e whilst counting rate morf e so th ecenr f pe thao t 0 n1 latter value are recorded when the source is moved to the side of the probe- 132 collimator system. SincemitI esrayy s with energie 1.3o t 9p s u MeV d ,an even higher, (the predominan rayty s havin energn ga 0.7f o y 8 MeV),a considerable increase in thickness of the lead alloy would be necessary to achiev satisfactora e y performance with this radionuclidee th . l Thial s si more true since its short physical half-life limits its use to early uptake tests in which measurements must be undertaken under conditions of relatively low uptak relativeld ean y high extrathyroidal radioactivity. ACKNOWLEDGEMENT Th eBelche. H advic . E guidancd thin r. i ean sDr projecf o e e tar gratefully acknowledged. 124 REFERENCES Cl) INTERNATIONAL ATOMIC EMERGF AGENCY a t isotopc A . . (Padova^ 1 ) (1961) 309; Minerva (1961nuc5 _ . ; l 4 )Ann . Radiol. _5_ (1962) 731-, Brit . J Radiol. . _35 (1962) 205: Int . .J appl . Radiât (19623 _1 . ) 167; Acta i"ber. radiol.-cancer (19627 1_ . ) 183; Aota radiol. (Stockh. (19628 _5 ) ) ?33 . J ;"beig e Radiol, 45 (1962) 511. (2) BELCÏÏER, E.H., GOMEZ-CRESPO, G., TROTT, W.O., TOTTER, H. Nucl.-Med. (Stuttg.) _4 (1964) 78. 125 Fig. l 6x606 °M a 3.1 h 11.5 0 0.75 b 10.8 i 13.5 P 3.3 c 18.6 j 0.2 q 4.05 d 12.8 k 1.3 r 3.6 e 7.7 1 1.7 s 0.7 f 9.0 m 10.2 t 5.0 g 0.2 n 1.75 u 6.4 126 Fig. 2 0) O) c I 2 u to • 100 _... 1 r "n ^•\ 789 10 11 90 r 9 D 4 Distance of source from axis (cm) 80 h- l 80 | Of i n k. 70 70 l en 60 c 6 l c. 5 D 50 ' O r 125T u i ' 40 40 | 1s Working distance ;25cm X 30 3 0 l < 1 Discriminator : 20 keV | 0 2 e 20 - o" l «___^— 131 T to 1 10 1 . * 125J 1 n a A -,- -' ' ' ' 1 1 1 SJL n._ir-t--i "12 10 8 6 4 2 0 2 4 6 8 10 12 Distance of source from axis (cm) Fig. 3 0» 4* (0 L. en c. +~ c. 3 o t < 100 r_^ - ———— »100 ——— •-^^î\— ^_ 07 ———————————— a ' ————————————————————————————————————— 9 10 r to 90 9 3 • CO Distance of source from axis (cm) 80 8 D 01 "Jo 70 7D Öl 60 60 c c 50 5nW 8 99mjQ 40 U0 Working distance :25cm X 30 3 0 Discriminator •. 100 keV ,0 0 20 20 ___——— _ 131 J 10 10 . . 99mTc L 0 l l l i i 2 1 0 1 8 6 t 2 0 2 U 6 8 0 1 12 Distanc f sourco e e from axis (cm) Fig. re O) C i 2 o n> X • — ' 1 , , 100 - 1 1 ^^•< 789 10 11 90 L • 9C CO • ' Distanc f sourco e e from axis (cm) CD 80 | 8 D 0» 70 70 •4-1 (0 t_ 60 60 C7» _C 4-^ 50 . 53 C E 47 u £0 l 40 Se "ÎO Working distance :25cm 30 3 3 a § u —— ^iji n MIN ' n ' """OT— TT^j f l 0 .---.-- L l 100 J 0——— ~^ _ 1 0 1 g S ? 1'-i CO 90 - ô 90 4 Distance of source f'Qirs axis (cnnl o 80 i 30 ] ! 0) 70 l 1 *•n») SO \ SO en c •*-• 50 -i 5 0 c 0 132 T o p 1 u 40 L l 40 p m 30 30 Working distance : 25 cm X Discriminator :60V 0ke 20 2 0 ; „„„«„„ 131f 10 — 91 j D . . 1321 o' • 5 A 3 2 °/o Axial counting rate ______Fig. 7 99mTc Working distance:40cm DiscriminatorV ke 0 10 : ———————1 13 99m 2345 °/o Axial counting rate ______Fig. 8 e 47S Working distance:40cm Discriminator: 100 keV 131 T °/o Axial counting rate ______Fig. 9 132T Working distancm c 0 4 e: DiscriminatoV ke 0 60 r: Half scale SPECTRAL REGION ASSESSMEN E INFLUENCTH P O T E F THYROIO D DEPT THYROIN HO D RADIOIODINE UPTAKE K.M. Wellman, J. Tieman and E.L. Saenger Nuclear Medicine Laboratory f Radioisotope Laboratory- University of Cincinnati Medical Center, Ohio, USA ABSTRACT This paper describes a sensitive technique for thyroid radio- nuclide uptake measurement f detectoro e us se s"base th wit n o dh large fiel vief o d w place contacn i d te subject witth nece f th he o k Th . technique depends on correction of the measurements for variation in detector-to-thyroid distance, whic s estimatei h e n termth i d f o s photo-pea o scattet k re pulse-heigh ratith f o o t spectrue th f o m scintillation detector pulses e observe,th d ratios being compared with those foun measurementn i d n phantomo s s with "thyroidst "a different depths» Two variants of the technique, one using a single- detecto e otheth rd rusinan ga dual-detecto r syste e describedar m » e resultTh f comparativo s e experimental studie f theso s e techniques and the ORINS standard technique in I and I uptake measurements are presented. These indicate that the single-detector technique offer n increassa sensitivitn i e abouf duale o y th 0 time2 t - d an s detector technique an increase of 300 - 500 times as compared with the ORINS technique with a concomitant increase in accuracy resulting from the inclusion of a correction for variation in the depth of the thyroid. The dual-detector technique is shown to offer particular 123 promise for I uptake measurements. A protocol for comparative studie thyroif so d radionuclide uptake measurement techniques based on measurements on terminal patients is described and results obtained on a single patient presented. Thyroid uptakes remai mose th nt frequently used radioisotope function tes nuclean i t r medicine l procedureal , f aecountino ° i 8 s5 andr gfo , likewise, considerabla r fo e proportio totae th lf o nradiatio n dose administered medically (l). Approximately a decade ago, the pioneering work of Brucer _ejt aj. led to the formulatio standara f o n d techniqu r thyroifo e d uptake which coul employee db d in almos y laboratortan y wit varietha equipmenf o y t (2) wele .Th l known ORINS 135 technique establishe da detector-to-nec k distanc s optimua m abouf c o eo t m5 2 t reduce inverse square counting effect positionind san g error d stilsan l maintain satisfactory counting statistics to obtain patient studies in a reasonable amount f timeo . This techniqu s beeha en widely adopted ;a repor . y Cresptb al b oej reviews results of an international survey of thyroid uptakes, finding wide use of the ORINS technique (3). In the latter studies, utilizing very controlled laboratoriee variablesth f o $ 0 ,8 s anothe e weron ef o withie rfoun b $ o 0 t dn1 in thyroid uptake estimation. Significant advances in instrumentation, plus a wider availability at reasonable costs over the last few years, would warrant a re-evaluation of presently used thyroidal uptake techniques. The ORINS method was postulated on the basis of the inverse square law such that at a 25 cm detector-to-neck (DTN) distanc thyroie th e d appeared satisfactoril poina s a yt source. Thyroid depth consideres wa negligibla d e variable wit minimaha l effec totae termn th i t lf o s counting distance. However, variations in photopeak attenuation and associated Compton scatter also results from variable amounts of tissue underlying the thyroid e ORINTh . S technique doet inherebtlsno y correc thesr fo t e variations. A revised uptake method which will inherently correct both for the -tr oto -thyroic dete d distance (DTD) hencd ,inverse an th e e square law wels ,a s a l the variable photopeak attenuation due to variable depths of the thyroid has pre- viously been proposed by our laboratory (4). In brief, the technique utilised detectors with a large field of view and an efficient geometry which are in contact measures wit i e surfacnecke n intercomparisoD th ha th DT .y f db o e f no photopea o scattet k r ratio a stud n i sy subject with those foun n standardi d , variable thyroid depth phantoms. In present study reports the results evaluating the effec variablf o t e thyroid depth phantomn si s simulating adul children'd an t s necks. Methods A 400 channel Packard multichannel analyzer was used in conjunction " Nal(Tl1 x " )1 uncollimatea wit ) (l h d crystal havin " leag1 d shieldin) (2 d gan dual 3" x 1-1/2" Nal(Tl) uncollimated crystal havine 1/4" lead shielding with their central axes at right angles as previously described. (4) . Spectra of a 10 fiCi I standard were analyzed for the 0.364 MeV photopeak, the scatter region spectrue th f o m belo Comptoe th w n e 0.3^valle th photopeakV 4f Me o y e th d ,an combined integra lphotopeae counth f o td scatte kan r regions. Thyroid neck phantoms with variable depth thyroid inserts simulating an adult (20 g) , 10 year 136 ) wernewbord yeag e an l on e( r , fabricateo t ng) 5 ( yea 5 d , ol rd g) fro0 ol(1 md poly-methylmethacrylate. Thyroid depths were e Th graduate . cm 5 n stepi d0. f o s principle studies were carried out in the adult phantom which is to the exact dimensions of the ORTTTS phantom with the modification of variable depth thyroid inserts deptm c h.8 2. inser(The t duplicate e ORINth s S phantoml m ) 0 (2)10 A . flask containin I standar0 jj.C1 i e gth d solutio f nfiberboaro place" 1 n o ds a d a scatter mediu alss mowa use r intercomparisofo d n since such phantom e usear sn i d many radioisotope laboratories. Comparative studies of the effect of thyroid depth in the phantoms as well as comparison with the 100 ml flask were carried out with both detector systemm c 5 2 s a placee surfac e t "neckth a th n d df o o ean " detector-surface distance. 121 Iodine-123 produce a cyclotro n e i d th Sb(a,2ny nb I reactio) n was evaluated in the adult phantom to determine the feasibility of correcting for thyroid depth compared to previous experience with I. A dual 3" x 1/4" Nal(Tl) crystal system with counterbalanced detector head was specially designed for use 123 with I. Iodine-123, with a monoenergetic gamma-ray of 159 keV a*id a 27 keV X-ray can be used very effectively with this 1/4" crystal with significantly less background counts than with thicker crystals. Results The mean effective thyroid depth, i.e. apparent centre of activity of the thyroid fronece th mk witm surfacec a h 6 adult3 5 2. n s e foun,i b s wa o t d median value of 2.8 cm (Pig.l.). The distribution is somewhat skewed to more superficially placed glands. Prom these data, an average effective depth in the adult phantom of 2.8 cm was used throughout the comparative experiments. In Table I, the results with the 1" x 1" Nal(Tl) detector are contrasted e standarth t A . d witm distancc h5 2 integraf o e l counting, thers i e positiva negativa d an ('fe$ uses e° a 0i erro3 erro1 d9 f indicatef ro ro s percentage erro uptake)f ro deviatiom ,c wit± a h n fro. meae cm th m n 8 dept2. f o h i5 °Photopea -1 error d an .% k 1 Thescountin +2 procedureo a etw e s th gha e sar most commonly used variant ORIKe th Sf o stechnique . Interestingly, integral counting has the least inherent error in thyroid depth is not taken into account . Surface counting wouls ,a anticipatede db , result mucn si h exaggerated errors whedistancem c n5 2 compare e th . o t Howeverd , counting e increaserateb n sca d approximatel 0 time2 y flas l m y surfacsb 0 k 10 doe ee scountingth cloself o e Us y. approximate the mean thyroid depth conditions for both photopeak and integral counting respectively$ 6 - d , an bein % 5 .g+ This latter finding also explains 137 a consistent mean difference of about 7 ^> previously found "between the results wit duae th hl crysta le standar systeth d an md uptake system. Similar results were obtained with the dual crystal system seen in Tabl . I eErrorthyroio t e sdu d depthcorrectedt no f abouf ,i o e sam e th te ,ar magnitude for 25 cm standard distance counting, but somewhat greater with the crysta" 1 x r surfac " fo l1 e counting witexceptioe th h integraf o n l countinn gi the 100 ml flask. However, the count rate is increased by a factor of 300 - 500 times with the dual crystal surface counting when compared to the 25 cm position crystal" 1 x " 1 .wit e hth Phantom studies utilizing I in Fig. 2 reveal a satisfactory linear response of the P/S ratio with thyroid depth. A similar linear response was also produce specialle th y db y developed 1/4dua" 3 l"x crystal system (Fig. 3.). It is noted that some change with time in the slope of the depth response line is due to an increasing influence of the contamination from 1 9 AI. Thyroid depth response has also been found to be linear, using the phantom with a Ge(Li) detector system (Fig. 4-). In age-specific thyroid neck phantoms (Fig. 5.)» linear P/S ratio depth responses are also found. It is evident that the adult phantom cannot be used satisfactorily with children. Discussion The analysis would suggest that an appreciable error of approximately 10 % can result in thyroid uptakes utilizing the standard uptake technique with integral counting. Paradoxically, photopeak or window counting leads to an even larger error, +21 The recent newcome famile th f iodino o yt r e radionuclides, nanel, I y 123 has very ideal characteristic sgammV witke ß-emissio o ah 9 (5)15 a . d nan Furthermore, its physical half-life appears to be optimum for the biological characteristic thyroidaf so l iodine uptake (6). 138 s intriguinIi t consideo gt possibilite rth e dosth e f o yreductio n that could result with use of 123I, i.e. about a factor of 100 with the increased sensitivity of the dual crystal uptake system (500 X)totalling to about a 5 x 10 reductio n dosei n . An automatic system which will greatly simplify the mechanics of using this more complicated techniqu presentls i e y being developed. However ,a smal l dual-channel analyze predetermined ran d standard depth-response graph eacr sfo h phantom coul usee db d very readily. Alstechnique th o readils i e y adaptablo t e a simple computer program (DULXTLTJP standare )slope th see Th f Tabln o e i n . d II e curv bees eha n highlfoune b o t dy reproducibl e incorporateb n ca d ean d inte th o computer program as well as into the electronics of the automatic uptake system. Furthermore, the constant slope only makes it necessary to make one thyroid neck phantom measuremen meae th n t tdeptha , i.e moro .n e than with other standard procedures. From evidens Fig.i t 5i t tha constanta t relationship exists between the age-specific phantoms such that constant computee th usee b n i dn rsca program to convert measurement adule th tn si phanto e specifiag o t m c results. Addendum Protoco cadaver lfo r studies The "standard" uptake system generall crysta" I yx consist" l1 a f so (collimated or uncollimated) and a 25 cm detector-neck counting distance. The standard iodinflasl m extrathyroidad 0 kan e 10 solutioa n i s ni l iodine activity is corrected for by using a "B" filter (4" x 4" * 1/2" piece of lead) placed over the thyroid. Variants to this technique use a high count (at 25 cm or on the surface) instead of the "B" filter to correct for the extrathyroidal activity. s discusseA n thii d s paper, variation thyroidan si l depth have some effect even on uptake measurements mad relativela BNDm c ed 5 ,an usin2 e gth y large effect on uptake measurements made using this "standard" system witcrystae th h n i l contact with the neck. However, there is a very large increase in sensitivity when surface countin usedcountina s g i d ,an g system utilizing surface counting S rati P/ ancorrec o dt a o thyroir fo t d depth variation bees sha n described. Comparison studies among the various systems are informative, but the ultimate tes eacf o t h system abilits woulit e determino db t y absolute th e e activity in a thyroid gland at any given time. The following protocol utilizing terminal patients with thyroid counting befor afted ean r autopsy whepatiene nth t expires has been set up for this purpose. 139 . 1 Prepar calibratea e solutionI d jjCi/ml ( ,conveniena s i l t concentration). . 2 Calibrat countine eth g system usee b couns o t do whict te har the thyroid gland following autopsy falcoA ( . n container with the known activity in 10, 20, 30 and 40 ml solutions was used for the data which will be given later) . calibratioa n Ru duae n3 .th curv l r crystafo e l system using 1 |iCi at depths of 1.8, 2.8 and 3.8 cm in the neck phantom. This curve represents CPM/|u.Ci vs. P/S ratio. 4. Determine the CPM/(j.Ci for the 1" x 1" crystal using 1 ^Ci in countinm c 5 2 a flasl g m d distance0 kan 10 a . 5. Administer approximately 10 j^Ci of I to terminal patient. (it does not need to be from precisely calibrated stock solution) . When the patient expires, make the following measurement prior to autopsy« 6a Determine P/S ratio for dual crystal uptake system: ) Photopea(a oveM kCP r thyroid ) Scatte(b oveM rCP r thyroid ) Photopea(c oveM kCP r thigh ) Scatte(d oveM rCP r thigh P/S . 6b Determin" "B e crystae" 1 th thyroi x d " lan usin1 M dCP e gth filte countinm c r 5 wit2 ha g distancet oveM CP r nec) (a k withou filte" "B t r (b) CPM over neck with "B" filter b - a Thyroi= M dCP 6c Determine thyroid CPM using the 1" x 1" crystal with a thigh count at both the 25 cm distance and on the surface of the thigh: oveM CP r nec) (a k (b) CPM 25 cm from thigh contacn o M CP t wit) (c h thigh Thyroid CPM = a - b and/or a - c Following autopsy, coun thyroie th t d precalibrate e glanth n di d detection appropriate systeth n i m e geometry. 140 8. From the above data the following calculations can be made: 8a Absolute thyroid activit divide7 e M fro. th CP y No m y db CPM/i^Ci determined in No. 2 for the appropriate geometry, 8b Absolute activit y duayb l crystal system photopea M ovekCP r thyroi da divideCPM/(^Ce 6 froth . y No mb d i founy db enterin calibratioe th g n curve determine wit3 . h No n i d the P/S ratio found in No. 6a. 8c Absolute activity using the 1" x 1" crystal and the "B" filter thyroid CPM from No. 6b divided by the CPM/jiCi found in No. 4« 8d Absolute activit e thigcrystay" 1 th usin x hd " lan g1 count. Thryoid CPM from No. 6c divided by the CPM/p,Ci found in No. 4» Results Followin e resultth e gar s froe patienon m tI give 0 jiCf 1 no i approximatel hour0 1 y s prio expirationo rt e onlTh .y deviation froprotocoe th m l collimate" 4 x " 4 a d f crystao e crystal" 1 us lx e " insteath 1 wa. n a i s f do . 1 Absolute thyroid activity determine countiny db e glanth g d following autopsy was .08 jiCi. 2. Absolute activity determined by the dual crystal uptake 6 |j,Cisyste.0 .s wa m filter" "B absolute e th th , d an e " . activit4 3 x " 4 Wit ye th h 3 |iCiwa.0 s , absolute th thige , th cm hd e 5 counan 2 . " t 4 4 a t x " 4 Wit e th h activity was .11 |,iCi. 5. With the 4" x 4" and the thigh count on contact with the thigh, the absolute activity was .08 REFERENCES PUBLIS U C ) HEALT(1 H SERVICE f Radionuclideo e Us , Survee th f o ys in Medicine, USPÏÏS Rep. BRH/DMRE 70-1 (1970). (2) BRUCER, M. Thyroid radioiodine uptake measurements; a standard syste r universamfo l intercalibration. USAEC Rep. ORINS-19 (1959). 141 (3) GOMEZ-CRESPO , VETTERG. , . H Int, . .J appl. Radiât (1966_ !? . ) 531. ) (4 WELLMAN, H.F., KEREIAKES, J.G., TEAGER, T.B., KARCHES, G.J., SAENGER, E.L . J nucl. . Med (196?8 _ .. 86 ) (5) MYERS, W. In "Radioactive Pharmaceuticals", AEC Symposium Serie6 (CCW-651111 . No s ) ,USAEC, Divisio f Technicao n l Information (1966) p. ?17. (6) WAGTCER, H.N., Jr., EMMOWS n "RadioactivI . H , e Pharmaceuticals", AEC Symposium Serie6 (COWF-651111) . Wo s , TJSAEC, Divisiof o n Technical Information (1966) p.l. TABLE l THYROID UPTAKE ERROR) (% S l" CRYSTAL M C DN5 2 D SPECTRAL FLASL M 0 K 10 PHANTOM - DEPTHS FROM MEAN (2,8 CM) REGION 1 CM +1 CM PHOTOPEAK +5 +21 -15 INTEGRAL -6 +13 -9 M C pN 0 D PHOTOPEAK +52 +49 9 -2 I INTEGRAL +34 +38 -24 " CRYSTAL3 x DUA " L1 S DND 25 CM SPECTRAL 100 ML FLASK PHANTOM - DEPTHS FROM MEAN (2,8 CM) REGION M C 1 - +1 CM PHOTOPEAK +25 +17 -17 INTEGRAL +7 +10 -11 DND 0 CM PHOTOPEAK +34 +41 -24 INTEGRAL +9 +23 -78 142 DULXTLUP ÜUAL CRYSTAL 1^1i THYROID UPTAKE INPUT PHOTOPEAK COUNTS FOR PATIENT'S NECK AND THIGH PHOTOPEAK COUNTING TIMES FOR NECK AND THIGH ICATTER COUNTS FOR PATIENT s NECK AND THIGH CATTER COUNTINJPfi G TIMES FOR NECK AND THIGH SCATTE'HOTOPEAR KCPt CPf MFO RFO STANDARR STANDARD D OUTPUT AND/O 1 THYROIH HOU2 R R D UPTAK) E(s TABLE 2 143 DISTRIBUTION OF EFFECTIVE THYROID DEPTH IN ADULT PATIENT POPULATION 20-1 15- Effective thyroid depth = distance from surface of nec o centet k f o r activity of each thyroid lobe 0) "o U_ 10- 0> jQ E 5- I- 4.5 4.0 3.5 3.0 2.6 2.1 1.8 1.5 1.2 0.9 0.6 Effective depth of thyroid in cm. HLg.l. 144 n 5 2. .THYROID-NECK PHANTOM CALIBRATION CURVE 123. (c and 1x3" Nal(TI) crystals) 2.0- o x 5 û. Ü 1.5- Photopeak /Compton Scatter 1.3 3.0 35 2.0 1.5 Fig.2. 145 ( 1.8) cm 3.0- PHOTOPEA SCATTEO T K R RATIO T INCREASINSA G THYROID DEPTHS123! (twol/4lx3MNaI(Ti) 2.8- crystals on neck phantc.n) (2.3) 2.6- 2.4- (2.8) IS 2.2H T0+38 hrs. 8 (3.3) <0 S (3.8) 1.8- I.6H 1.4- (3.8) 1.8 4 1 1.7 5 1 16 1.3 1.2 PHOTO PEAK SCATTERTO Fig. 3. 146 1.90 n THYROID-NECK PHANTOM 4 (1.8) CALIBRATION CURVE WITH 1.55- d Ge(Li123an 1 ) DETECTOR 1.40- o 1.25- A (2.3) X 2 a. 1.10- u .95- A (2.8) .80- A(3.3) .65- \A (3(3.8. ) .700 .600 .500 .400 .300 Photopeak/Scotter Pig. 4. 147 I2H THYROID-NECK STANDARDS 0.8cm (Age Specific -O.I/jCi l311 ) 1.3cm 10- ONE YR. 1.8cm IOo X a. o ADULT-3? 5- 2.8cm m c 8 3. 0 0.8 0.7 0.6 Pig. 5 148 METHO MEASURINF O D G THYROID 1-131 UPTAKE BA YDIGITIZE D SCIPTIGRA P THYROIMO D GLAND . . SaegusKakehK ÏÏ d an ia Departmen f o Radiologt y Chiba University Schoo f Medicino l e Chita, Japan ABSTRACT This paper describes a method using a dual-detector scanne on-lind an r e compute r measurinfo r e latth g e uptake of I by the thyroid. The method can be applied during routine scans of the thyroid and was found to give results n generai l agreement with those obtaine e ORIÏTth y Sdb standard method. 1. Introduction n efforIa n o obtait t e thyroith n d 1-131 uptak y processb e - e digita th e datin th n go a l scintigra f thyroio m d glandn a , experimen s beeha t n carried out. Using an on-line computer system, by which the total counts of a certain area can be calculated briefly, the thyroid 1-131 uptake measurement, was made from routine scan data of thyroid gland. 2. Method e scanneTh r user thyroifo d d scanning consisto tw f o s detectors facing each other above and below with the 5"0 x 2" Nal Crystal. It is a kind of the whole body scanner, from which two systems of the positioning signal of the detector (X, Y) and the output signal (Z) can be taken out. These data are memorized in the 4K words computer (HITAC 10). The sampling of output signale e donb th n er ca witsfo e interva m th h 1m f o l scanning directio e , 6----m4 th X direction ( , nr 2 fo f m o d an ) spacing direction (Y direction). In the thyroid scanning a scan matri s madi xy samplinb e e e arecount th f th eacgo a n i hs 4 x 4mm. The scan area of the thyroid gland ranges between around 10 x 10cm and 15 x 15cm and the number of whole data points is 600 to 1300. The scan matrix is displayed by CRT and the whole e arecountth an i containins e thyroith g d glane ar d calculated by the program, which is used to obtain the total 149 counts in a certain rectangle, and typed out. The thyroid sca s mad nwa n patient o e hour4 2 s s aftee th r administratio e sam- SO^uCth 0 ef t 1-1314 o ia tim f e o d n th ean , data were put into the computer memory. The scan conditions are as follows : Scan speed: 50cm/min. Spacing: 2mm Collimator: Focusing distance: 7.5cm Numbe 3 holesholef o r16 s: Typ e: Honey cone type Measurement: Photo peak of 1-131:364 keV Window width: 100 keV Standard source: 1-131 capsule containing the same dos s administerea e patientso t d . Neck phantom: ORINS type The phantom scan was made with the same conditions as the patient backgroune anth d d data were obtaine e samth et a timed . 3. Results obtained ) Basi(A c experiment Two acrylic neck phantoms (ORINS type) were used a thyroi; d gland phanto x 6cm* 6 ( m) mad y filteb e r paper with 50;aC f 1-13o i 1 f thed o SOjuCt intan me f 1-13pu o ion o s wa 1 capsul s placeewa d e other ie th ncompute Th . r sca s don nwa n eac o ef themo h . Then th e scae th e clearance sizeffecn th f th o eare d f o tan a e under the pinhole collimato e totath ln o r count s investigatedswa . Also the dependence of the thyroid uptake on the depth of thyroid glan s examinedwa d . ) Relationshi(1 p between sca summins nit ared gan a counts. In the routine thyroid scanning the scan areas generally range from 10 x 10cm* to 14 x 14cm . The scan matrices were determined as follows: The maximua m area is 14 x 14cm2 , and on the area f 12.x 7.6cm"o s 6 4x 12.4 7. ,d ,an 10. 2 9. 8x 10.8 x 2 ,9. respective summing counts were calculated. The area of 7.6 x 7.6cm* e smalleswoulth e b d t size whicn i , h thyroid imagn ca e jus e fitb t . Fig. 1 show e relationshith s p betwee e scath n n nece th arek f o aphanto m with thyroi ds summinsourcit d gan e counts with 6cm clearance as well as the relationship between the sca necne th arek f o phantoa m with standards sourcit d an e summing counts wite samth he clearance e summinTh . g countf o s both sources decreas numbee n sami eth en i rinclinatio e th s a n area decreases x e 14cmarecounte th 4 th s take1 a i af f o sI .n e 100% tb ox 7.6cm 6 e count,7. th * n decreasi s y 121b e . From tne result obtained it is certain that the scan area should be as large as possible. However, since the total counts 150 of the thyroid and standard sources decrease in the same inclina- n expecca tion e correce th t,on t resul e tsmal th eve n li n area, if only the thyroid gland is contained and the total counts of the thyroid and standard sources are compared in the same area. (2) Change in the summing counts due to the difference in the clearances. Th es selecteclearancwa m a standare 6c s th a d f d o e an d distance was increased and decreased by 4cm from the standard point. Frodigitizee th m d e necscanth k f o sphantom s with thyroid and standard sources the summing counts were calculated. e datTh ax 14cm e showobtaine4 1 ar e are3 n Fig th f i no a . n .2 i d e summinTh g counts decrease slightl e clearancth s a y e increases. In the smaller areas the tendency is almost the same. e ) summinChangth (3 e n differenci eth g e o countt th e n i du se dept f thyroio h d gland. The thyroid glan s thii d n compared with other e organth f o s body and located near the skin surface. The absorption and scattering of gamma-rays by tissues are relatively small. The relation between the depths of thyroid glands and the uptake values was investigated, by the ORINS standard method and the digitized scan technique using neck phantoms. x 6cmTh 6 e thyroie depthth f o sd gland source were changed nece ith nk e thyroiphantoth d 3 dan m uptake values were calculated o 2.5c t depthe e rang1 th m th f f o froo sen e I th m(Tab . 1) . surfac e thyroith e d uptakes decrease essentiall straigha n i y t decreasins lineit d ,an g rat r 4mmn this abouI i pe e . s1 5 t experiment the thyroid uptakes obtained by the digitized scan technique were in agreement with those by the ORINS standard method. (B) Clinical cases patient0 O3 n o underwenwh s e thyroith t d scannine th g digitized scan was carried out (Fig. 3). From these data the thyroid uptakes were calculated and compared with those obtained ORINe bth y S standard method e resultTh . s were show n Figi n . .4 Of 30 cases, 5 cases which are plotted by the symbol^ were determine y addinb d e signale uppe th gth d lowe an rf o sr detectors. In other 25 cases (symbol: • ) the thyroid uptakes were calculated with the upper detector alone. The data obtained are scatterd about the 45 degree straight line through the origin. Among 25 cases of the difference between the thyroid uptakes determine e digitizeth y b d d scan techniqu e ORINth d S an estandar d method e greates,th t whole differencth ef o % s 8.1%76 i e t ,bu cases give the difference within + 5%. 4. Discussion digitizee Bth y d computer processin scintiscae th f o g n matrix, many clinical data such as the scintigrams, the image 151 processing e summinth , g count a certai f o s n area etce ar . obtained in a single test. Accordingly the burden to patients is reduced n thiI .s experiment e metho,th n whici de th h thyroid 1-131 uptake measuremen e donb en ca simultaneouslt y with a scintigram is studied. There was some disagreement between the thyroid uptake values obtained by the two method in clinical cases. This disagreement must have come froe facth mt thae routinth t e scan data wer t inte computepu eth o r memory. Accordingly scan areas wer t alwayno e e same n th somsI .e casee thyroie imagth th sf o e d t locatee centerno glanth s t t locatea wa d ,bu a corne n i df o r the matrix r thiFo s. reason errors would have been made evef i n the area of the scan matrix was the same. On the other hand, since the accuracy of mechanism of a scanner might be one of the factors of the error in this technique, the stability of the scan speed and the width of spacing should be checked closely in advance of performing tests. 5. Summary The method of measuring thyroid 1-131 uptake by the digitized scan matrix is one of the simple and good methods. It can be carrie utilizint ou d e routinth g e scan datae uptakTh . e values obtained by this method agreed well with those by the ORINS standard method. PEFERMCES (1) TAUXE, W.N. J. nucl. Med. _10 (1969) ) (2 ARIMIZU , MORRIS,N. , A.C nucl. .J . Med (1969O .JI ) 265. (3) SCHULZ, A.G., HOLLO, F.D. J. nucl. Med. 11 (1970) 508. 152 o± tne UKiNb btana- uigitizea scan Ratio id Gland ard Method Technique 1 . 0 cm 57.1% 56.7%0.993 1.5 55. 4 54.8 0.989 1.8 53. 5 53.0 0.991 2.1 51. 2 50.9 0.994 2.5 49. 4 50.2 1.016 Tab 1 Compariso. n betwee e Thyroith n d Uptake Values obtained by the ORINS Standard Method and Digitized Scan Technique True value of uptake 53.3% x 14c 4 1 mCounting area Clearance 6cm 100 ^ 100% -****** BO- 'S Clearance : 6 cm <§ —Standar~ o d source £60- — »—Thyroid phantom £ 1 J40 "6 Si • 20- 7.6x7.6 92x92 10.8x10.8 124x124 140x140 etif 1 . 0 50 100 150 200 250^ Scan Area Cl" Fig 1 .Relationshi p betwee scae th nne th are f ao neck phantom with 1-131s sourcit d an e summing counts. 153 JOO --0--< 100% 80 Counting oreo : 14* !4 cm* ô - - o- - Standard source i60 — •— Thyroid phantom E 3 W 40 o 20 24 0 61 12c 8 m Clearance Fig. 2 Relationship between the clearance and the summing counts in the scan area. M.M. m. T.U. 39% S.K. m. T.U. 64% Standard sourx* CI. 6cm = 69.6% Fig. 3 Images of thyroid gland and standard source in digitized scan matrices. 154 • :upper detector alone uppe: lowera r detectors % 80 O T 0 6 0 5 0 4 0 3 0 2 0 1 0 24hr. T.U.withORINS Standard Method Fig. 4 Correlation between the 24hr 1-131 thyroid uptake with ORINS standard method and the thyroid uptake with digitized scan technique. 155 THYROID 1-131 UPTAKE MEASUREMENT WITH A SCINTILLATION CAMERA H. . SaegusKakehK d an ia Departmen f o Radiologt y Chita University School of Medicine Chiba, Japan ABSSRACT This paper describes experimental and clinical studies aimed at the development of a method using a gamma-camera with a pin-hole collimato measurinr rfo thyroide th late y b gth e .I uptak f eo Attempts to measure uptake under the condition used for thyroid scintigraphy, namely wit e surfaccollimatoe hth th f o e workina t ra g fro m surface nece c th m5 th distanc k f - gavo e2 ef o evalue s significantly lower than those obtained by the ORINS standard method, the difference valuebetweeo tw workina e st th nA reachin g. $ distanc 8 g3 e scintigraphm c 5 2 lonteo - n o0 s f2 rywa practicabl statistie th d an e - cal errors in the measured uptakes were larger because of the reduced counting rates, but the values obtained were in general agreement with those obtained by the ORINS standard method. 1. Introduction o obtaiT scintigraa n thyroie th f mo d pland wit scintia h - camera ,pinhola e collimato usualls ri y use enlargo t d e th e image of thyroid gland which is small compared with other body organs. If the thyroid 1-131 uptake measurement is made simultaneously with the scintipram of the thyroid gland, it would be very convenient for us. This method has already been tried by some persons. However, the problem is whether or not we can achieve correct results with this method. Some experi- men bees tha n carrieusiny b t scinticamera g ou d a wit pinholha e collimato studo rt thyroie yth d 1-131 uptake measurement. 2. Method of Experiment The instrument used is a Nuclear Chicago's scintillation canera Pho/Gamma III with a pinhole collimator of 4.8mm diameter. The conditions of the thyroid uptake measurement with a scinti- same camer taî'injs th a e e aar ? scintiphotos, namel e 1-13yth 1 vain peak of the gamma energy of 364 +45 keV is used for both cases. The results obtained were compared with the routine thyroid uptakes. 157 Abasia s c experimen dise kind4 tth k f sourceo s filtef so r paper with SOuC f 1-13o i 1 were employed diametere Th . f theo s n arc 2, 4, 7 and lOcn. The relation between the clearance under collimatoe e botto th th countine f th o m d an rg rate s examineswa d (Fig. Thre1) . e kind 1-13f so 1 filte rshap e papeth f eo n i r thyroid gland were made and placed in the ORINS type neck phantom. e relationshipTh s betwee clearancee th ncountine th d an sg rates *s stated before «rare investigated to see their effect on th* uptakes. As a clinical experiment the uptake measurements were differeno tw curriet e a th t tt d ou a clearances s i e on e ,th distanc 20-25cm t e othef 2-5craa shore eo th th s ri d tn I an ,. distance method, as the thyroid gland is shaped large enough in the visual field of the detector, the room background counts» instead of the body background counts, were subtracted fron the patien e countnece th th k f r so phantoto m wit standarha d source» on the other hand, in the 25cm distance method, a part of the body is taken into the visual field of the detector. The B filter method is used and the body background counts are sub* tracted instearooe th m f backgrouno d d counts. 3. Pesults obtained Basi. A c experiment effece Th clearance changf ) o tth (1 n i e e upo thyroie nth d uptakes. A 1-131 disk diametem sourc2c f eplaceo s rwa d right under the pinhole of the collimator, and the counting rate was measured changin clearancee th g e countTh . s decreas numben i e r by the distance inverse square law. They rapidly decrease in numbe arouno t distancm p ru 6c d thed ean n relatively slowly. In the practical thyroid gland scintigraphy the clearance is usually 2 to 5cm, and so the change in the counting rates is high in the neighborhood of this point. For example, if there m clearance3c imeasurine a s th change n i ,th m ge1m erro+ f ro e countininth g rate25oe th case n sf th eo wil n I l . reac7% h+ clearance, if the same change in the counting rates is allowed, measurine th g error wil8mm* consequenca e lb s . A correce th e t measuremen clearance"ie th f to s require shore th tn i ddistanc e method. Next clearancee change ,th th countine n th i e d an sg rates is investigated whe e 1-13nth 1 source size changede ar s n I . Pig. 3 the change in the ratio of the counting rates of each disk source to those of a point source is shown. For the clearance above 20ccountine change th th m n i e g rate smals i s l enough to be neglected. However, when the clearance is 3 to Soi e differencth countine th e b n ei t gno raten ca largs i sd an e neglected. As the diameter of the source becomes larger, the counting rate reducee ar s thid an ds factor causes errorsf I . e sourcth s largeei sensitivite ,th detectoe e th th f o yn i r periphere centeth d ran y will differ from each e otherth d ,an counting rates will decrease as a whole. 158 crystae image th ) th Siz n (2 o ef le o countine surfacth d an eg rate. e advantag Th shore th tf o edistanc e metho scintigraphr fo d y consist e improvementh n i s f resolutioe imago tth o et e du n enlargement and the increase in the counting rate. However, the counting rat alss i e o effectee sourcsizee th th f eso y d b and the image on the crystal surface. As the source becomes larper, and the clearance smaller, the image size on the crystal wil enlargee e countinlb th d an dg rate reduced. Figur show4 e above-mentionee sth d relationship. Namely, e imagth e sizes i indicate m c e e sidlengt on n th i e f y o hb d plotted along the abscissa against the ratio of the counting rates alon e ordinatth g r threfo e ee 1-13kindth f 1o s filter paper phantoms of the thyroid gland with the clearances of 6, 10, 16 and 21cm. The large, medium and small sizes of the thyroid phantoms are 8 x 8cm, 6 x 6cm and 4 x 4cm respectively e 1-13th d 1an capsul standara uses i es a d d source. e e countinratioTh th f o s g rate variout a s s clearanceo st the standard source were measured. In the case of the large sized image the ratio of the counting rate is low. For example, e crysta th x 22c whe% n e 2 e ratiimago m2 65 lth th n s s i i oe surface (Fig. 5a), As the image sise becomes smaller (Fig. Sb), the ratio approaches 100%. Accordingly, v/hen the thyroid uptake measurement is rcade by using a scinticarcera, the clearance shoul e largdb e enoug o attait h correca n t valuestandara f I . d source having almos e sam th tpatient'e th siz s a e s thyroid gland is used, the correct answer will be obtained. However, therproblea s ei m tha standara t d e suitablsourcth f o e e size should be made at each measurement. Clinica. B l experiment patient3 O2 n whoo t s m 40-80uC f 1-13io capsulen 1i s swa administered per os, 24 hour thyroid uptakes were determined routine bth y e thyroid uptake measurement. Withi minute0 3 n s after this measurement, the thyroid uptakes were taken again by the short distance method and the 25cm distance method using a pinhole scinticamera. The results are shown in Fig. 6, and 7. In the short distance method the thyroid, uptakes are low compared with the routine method, and the maximum difference reached othee 38%th rn . O e 25c handth m n ,i distanc e method the counting rates become smaller and the statistical errors larger. However e dat,th a obtained agree well with thosf o e the routine method admitting the statistical counti^P errors. 4. Discussion e shorIth f t distance method whicn , i clearance hth s ei 5cmo t obtain useds 2 i ,ca thyroie e ,nth w d scintigrapht ya the same time. Put it is difficult to determine the correct uptake owing to the error made in measuring the distance, and 159 e differencth e betwee e countinth n ge cente rateth d t a ran s the periphery on the crystal surface caused by the image en- largement. The condition of the neck sfcin surface varies in each case and the error of a few millimeter can be easily made measuremene th n i f clearanceo t e sensitivitTh . e th s a y function of the source position is expressed as follows: Zd2 2 7 A*Hi *. ffZ 6* j where S: Sensitivity Diamete: d pinhole th f o re 1: Distance between the point source and the center d: Distance between the pinhole and the point source y thiB s formul sensitivite ath poine m aparth 3c t a yt froe mth center, whic locates hi belom pinholee 5c d wth calculates ,wa d and obtained the value of 63%. As the clearance becomes smaller, the sensitivity of the periphery of crystal lowers. When a point source lik capsula e standara uses i es a d uptakee th d s will be smaller than those obtained by the routine method. If a standard source same , th whicpatient'e s th siz hha s a e s thyroid gland, is used, the correct uptake will be expected. In the 25cm distance method the measurement of the distance and the enlargement of the image meet no problem. However, the counting rate is usually reduced and the accuracy of measurement becomes lower. To cover the disadvantage, it is necessary to tak longea e measuremente rth timr fo e , 5. Summary (1) Basic and clinical experiments on the thyroid 1-131 uptake measurement were carried out using a pinhole scintillation camera. (2) In the short distance method, in which the thyroid uptake measuremen same th made e b t a timen ca te wit e thyroihth d scintigraphy valuee ,th s obtaine generan i e comparew dar llo d with the routine method. It cannot be expected that a correct thyroid uptake is determined by this method. (3) It is recommended that the thyroid uptake measurement is made separately from the thyroid scintigraphy by the 2Sen distance method. REFERENCES (1) MALLARD, J.R., MYERS, M.J. Phys. in Med. Biol. 8 (1963) 165. (2) BRUCER, M. Thyroid radioiodine uptake measurements. A standard syste universar fo m l intercalibration. USAEC Rep. ORINS-18 (1959). (3) ANGER, S.O. In "Instrumentation in Nuclear Medicine" (UNE, G.J., Ed.) Academic Press, New York (196?) p. 485. 160 Cttttol i t i o \ \ QMranct \ \ \ 2cm0 disc tout» {200 I SQpCi'" ( ) Pin hota CoHinotor ISO 100 Thyroid 50 46 m c K 8 2 1 10 ClMronce Fig. 1 Schematic diagram of the thyroid 2 FigPercen. t counting a 2cm(rat f 6o e uptake measurement using a disk sourc f 1-13o e 1 (SO^uCin i ) scintillation camera with a air against clearance beloa w pinhole collimator. pinhole collimator. to%o crystal 80 i 60 clearance o O disc sourc airn i e( ) 40 1I 50jiCi 20 0 2 5 1 10 25 30 cm Clearance Tig. 3 Percent counting rate of 1-131 disk source to a point source against clearance belo e pinholth w e collimator r threfo e disk sources. M i loo __ _ k IM. L ^ s L^ ~~~~~~~~~~M » — | 80 •r^~^— ^^ CZ^So* length |eo L \ /' '¥., | 40 !_ clearance Sizes of Thyroid Phantom /^f] 6cm m s 4c : x 4 " 0 I © L : 6« 6cm ^ 16 - 20 8* 8cm 2l • M: 0 2 22c m8 1 6 1 4 1 2 1 0 1 8 6 4 2 Geometrical Image Length on Crystal Surface Fig. 4 Percent ratio of measured uptake to true uptake against geometrical image e crystalengtth n o hl surface. 162 1311 SOjiCi Clearance 21 cm Clearancm c 6 e Sizes of Thyroid Phantom M b. a. Fig. 5 Scintiphotos of thyroid phantoms containing SOpCi of 1-131 takepinhola y b n e scintillation camera. 163 % Short Distant Method 80 25 cm Distant Method 80 (2~5cm) 70 70 § 60 <36° o u o 50 c 50 c ix o 40 o40 t O3 3 3 30 i— 30 = 20 i 20 \» oj 10 0 10 20 30 % 48O 0 0 57 0 0 66 0 0 75 0 O 804 % 0 3 0 2 0 1 0- 24 hr. T.U. with Standard ORINS Technique 24 hr. T.U. with Standard ORINS Technique Fig. 6 Correlation between the 24hr 1-131 Fig. 7 Correlation between the 24hr 1-131 thyroid uptake with a pinhole thyroid uptake with a pinhole camera and the uptake with the camera and the uptake with the standard ORINS technique. standard ORINS technique. SELECTED BIBLIOGRAPHY ALBAREDE, P., DI PAOLA, R., CROSSARD, M. Collimateur à champs multiples pou mesur a fixatioa l rl e ed n thyroïdienne, Ann. Radiol .8 (1965 ) 685» ALEXANDER, W.D., HARDEN McG.. ,R , McLARTY , SHIMMINS,D. Thyroida, ,J. l suppressibility after stopping long-term-treatmen thyrotoxicosif o t s with anti-thyroid drugs, Metabolism 18 (1969) 58. ALEXANDER, W.D., HARDEN McG.. ,R , SHIMMINS , Studiethyroie ,J. th f so d iodide "trap" in man, Recent Progr. Hormone Res. 25_ (1969) 423. ALEXANDER, W.D., HARDEN McG.. ,R , KOUTRAS, D.A., WAYNE Influenc, ,E. f eo iodine intake after treatment with anti-thyroid drugs, Lance i (1965i t ) 866. ANDROS, G., HARPER, P. 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