Eur e opea icin n Association of Nuclear Med

Parathyroid Scintigraphy A Technologist’s Guide Contributors

Nish Fernando Sylviane Prévot Chief Technologist Chair, EANM Technologist Committee Department of Nuclear Medicine Chief Technologist St. Bartholomew’s Hospital, London, UK Service de Médecine Nucléaire Centre Georges-François Leclerc, Dijon, France Dr. Elif Hindié, MD, PhD Service de Médecine Nucléaire Domenico Rubello*, MD Hôpital Saint-Antoine, Paris, France Director Nuclear Medicine Service - PET Unit Sue Huggett ‘S. Maria della Misericordia’ Hospital Senior University Teacher Istituto Oncologico Veneto (IOV), Rovigo, Italy Department of Radiography City University, London, United Kingdom Audrey Taylor Chief Technologist José Pires Jorge Department of Nuclear Medicine Professeur HES-S2 Guy’s and St. Thomas’ Hospital, London, UK Ecole Cantonale Vaudoise de Techniciens en Radiologie Médicale (TRM) Linda Tutty Lausanne, Switzerland Senior Radiographer St. James’s Hospital Regis Lecoultre Dublin, Ireland Professeur HES-S2 Ecole Cantonale Vaudoise de Techniciens en Radiologie Médicale (TRM) Lausanne, Switzerland

* Domenico Rubello, MD is coordinator of the National Study Group on parathyroid scintigraphy of AIMN (Italian Association of Nuclear Medicine) and is responsible for developing study programmes on minimally invasive radioguided surgery in patients with hyperparathyroidism for GISCRIS (Italian Study Group on Radioguided Surgery and Immunoscintigraphy)

Acknowledgement for the photo: P. Lind, Department of Nuclear Medicine, LKH Klagenfurt, Austria

 Imaging. Medical Squibb Bristol-Myers of necessarily not and authors the of those are expressed views The wasThis booklet sponsored by aneducational grant Medical from Squibb Bristol-Myers Imaging. References Rubello Domenico Chapter 6– forTechnical parathyroid surgery adenomas of probe-guided aspects FernandoNish andSueHuggett protocolsChapter 5–Imaging Audrey Taylor Fernando andNish Chapter 4–Patient preparation PiresJosé Jorge andRegis Lecoultre equipment–preparationChapter 3 –Imaging anduse Linda Tutty Chapter 2 –Radiopharmaceuticals Elif Hindié Chapter 1 –Applicationsofparathyroid imaging Sue Huggett Introduction Sylviane Prévot Foreword Contents

 33–39 29–32 24–28 18–23 13–17 40–43 6–12 5 4 EANM Foreword Sylviane Prévot

Today the notion of competence is at the to Bristol-Myers Squibb Imaging for their con- heart of professional development. Technol- fidence and generous sponsorship. ogists’ specific professional skills of working efficiently and knowledgeably are essential Efforts to image the parathyroid gland date to ensure high-quality practice in nuclear back many years. I hope this brochure will be medicine departments. useful to technologists in the management of patients with hyperparathyroidism and will Since they were formed, the EANM Tech- benefit these patients by optimising care and nologist Committee and Sub-committee on welfare. Education have devoted themselves to the improvement of nuclear medicine technolo- Sylviane Prévot gists’ (NMTs) professional skills. Chair, EANM Technologist Committee

Publications that will assist in the setting of high standards for NMTs’ work throughout Europe have been developed. A series of bro- chures, “technologists’ guides”, was planned in early 2004. The first of these was dedicated to myocardial perfusion imaging and the current volume, the second in the planned series, ad- dresses parathyroid imaging.

Renowned authors with expertise in the field have been selected to provide an informative and truly comprehensive tool for technolo- gists that will serve as a reference and improve the quality of daily practice.

I am grateful for the hard work of all the con- tributors, who have played a key role in ensur- ing the high scientific content and educational value of this booklet. Many thanks are due to Sue Huggett, who coordinated the project, to the members of the EANM Technologist Sub-committee on Education and particularly

 a different filter if the total counts are low. with another protocol or when we may need imaged be to need may and subtraction for enough long for flat lie cannot who patient the fore.g. analysis, or acquisition in applied, and how various protocol variations should be when know to order in needed is strategies certain using for rationales the of Awareness improves compliance as well as satisfaction. whynecessaryisit tolieawkwardin positions explainwhycertain foods mustavoidedbe or alwayscareisparamount, beingandableto patients,to theircarers andother staff. Patient nologist to communicate accurate information for wise decision making. It also allows the tech ing for the technologist and can form the basis understanding of the techniques that is satisfy Knowledge of imaging theory provides a deeper of thosefor whomthisistheirfirstbook. peating, and so I will do so here for the benefit certain things I wrote for the last book bear re of patient care and equipment use. I think that and rationale of imaging with the practicalities theory the havecombined weWe that hope what we hopewillbeaseries. parathyroid imaging, thesecondbookin us againthisyear to produce thisbookon grateful haveare thatthey very sponsored imaging for technologists.perfusion We in2004wasabookonmyocardialSquibb gist Committee sponsored by Myers Bristol The firstpublicationoftheEANM Technolo Sue Huggett Introduction - - - -  enabled andencouraged. is practice and theory of integration the that so needed is it when and as information ful help provide will booklet this that hope We not, given. was but been, have should credit which for material used inadvertently have we if gise apolo We identifiable. are authors original where given been have references and cols, sources for information, not least local proto of number a to indebted are authors The practices. working thoughtful more to leading thereby them, behind rationales the explain and plement sup hopefully will but protocols these plant sup to meant not is Guidelines. booklet This EANM the of terms broader the within even departments, between vary will Protocols - - - - - EANM Applications of parathyroid imaging Elif Hindié

Primary hyperparathyroidism deeply modified the clinical spectrum of the Primary hyperparathyroidism (pHPT) is a disease at diagnosis (Heath et al. 1980). Most surgically correctable disease with the third new cases are now biologically mild without highest incidence of all endocrine disorders overt symptoms (Al Zahrani and Levine 1997). after diabetes mellitus and hyperthyroidism Parathyroidectomy is the only curative treat- (Al Zahrani and Levine 1997). Through their ment for pHPT. In the recent guidelines of the secretion of parathyroid hormone (PTH), the US National Institute of Health (NIH), surgery two pairs of parathyroid glands, located in the is recommended for all young individuals and neck posterior to the thyroid gland, regulate for all patients with overt symptoms (Bilezikian serum calcium concentration and bone me- et al. 2002). For patients who are asymptom- tabolism. PTH promotes the release of calcium atic and are 50 years old or older, surgery is from bone, increases absorption of calcium recommended if any of the following signs from the intestine and increases reabsorp- are present: serum calcium greater than 10 tion of calcium in the renal tubules. In turn, mg/l above the upper limits of normal; 24-h the serum calcium concentration regulates total urine calcium excretion of more than 400 PTH secretion, a mechanism mediated via a mg; reduction in creatinine clearance by more calcium-sensing receptor on the surface of than 30% compared with age-matched per- the parathyroid cells. pHPT is caused by the sons; bone density more than 2.5 SDs below secretion of excessive amounts of PTH by peak bone mass: T score < -2.5. Surgery is also one or more enlarged diseased parathyroid recommended when medical surveillance gland(s). Patients with pHPT may suffer from is either not desirable or not possible. After renal stones, osteoporosis, gastro-intestinal complete baseline evaluation, patients who symptoms, cardiovascular disease, muscle are not operated on need to be monitored weakness and fatigue, and neuropsychologi- twice yearly for serum calcium concentration cal disorders. The highest prevalence of the and yearly for creatinine concentration; it is disease is found in post-menopausal women. also recommended that bone mass measure- A prevalence of 2% was found by screening ments are obtained on a yearly basis (Bilezikian post-menopausal women (Lundgren). et al. 2002). Some authors recommend para- thyroidectomy for all patients with a secure In the past, pHPT was characterised by severe diagnosis of pHPT (Utiger 1999). skeletal and renal complications and apparent mortality. This may still be the case in some Successful parathyroidectomy depends on developing countries. The introduction of recognition and excision of all hyperfunc- calcium auto-analysers in the early 1970s tioning parathyroid glands. pHPT is typically led to changes in the incidence of pHPT and caused by a solitary parathyroid adenoma, less

 vention, including the number and location of have all information concerning the first inter et al. 1993). In these patients it is tonecessary tent or recurrent hyperparathyroidism (Weber ing method of choice in reoperation of persis et al. 1989) has been established as the imag et al. 1998). therefore mandatory before reoperation (Sosa increase in surgical complications. Imaging is dramatic reduction in the success rate and an Clark 1989). Repeat surgery is associated with a and (Levin MGD undetected and scended) unde or artery, carotid the of sheath the in (retro-oesophageal, mediastinal, intrathyroid, glands ectopic are surgery failed for reasons patients (Russell and Edis 1982). The two main of 90–95% cureachievedin neck, the in sites potential all dissecting exploration, bilateral Unguided surgery. beforefirst-time used not For several decades, preoperative imaging was before ismandatory reoperationImaging thyroid glands. exploration with identification of all four para routinebilateralin consists surgery ventional Con 2002). al. et (Marx hyperparathyroidism docrine neoplasia type 1 or type 2a or familial with hereditary disorders such as multiple en sporadic, while a small number are associated are MGD of cases Most glands. parathyroid four all or three of hyperplasia or adenomas double either have MGD with Patients ma. carcino parathyroid by cases) of 1% (about rarely and (MGD) disease gland parathyroid multiple by cases) of 15% (about frequently 99m Tc-sestamibi scanning (Coakley ------ ing whereabouts in the neck to start dissec start to neck the in whereabouts ing now appreciate having information concern would surgeons Most hyperparathyroidism. cure to time best the is exploration first The parathyroidectomy ordered onaroutine basisfor first-time with Scanning proceeding to reoperation. and CT or MRI for a mediastinal image) before technique (usually ultrasound for a neck focus imaging second a with confirmed be should that opinion author’s the is focus.It mediastinal a for especially ful, use whenever SPECT and neck, the of views by using both anterior and lateral (or oblique) surgeon with the best anatomical information protocol is used, it is necessary to provide the Whichever glands. surgeon and the size and histology of resected parathyroid glands that have been seen by the surgeon to find the offending gland earlier in the allowing By 1997). al. et (Hindié surgery bilateral of duration the shorten also would imaging Preoperative 2005). al. et (Liu gland elusive the for search the in surgery neck extensive initial unnecessary avoiding copy, proceed directly with first-intention thoracos can surgeon the gland, mediastinal a of case the al.In et 1997). (Hindié to100% close very reach now can surgery bilateral of success the preoperatively,recognised are tumours parathyroid ectopic of (2-5%) cases rare the glands (Sosa et al. 1998; Liu et al. 2005). When tion and the possibility of ectopic parathyroid Chapter 1:Applications ofparathyroid imaging 99m Tc-sestamibi isincreasingly 99m Tc-sestamibi scanning Tc-sestamibi 99m Tc-sestamibi resultsTc-sestamibi - - - - EANM the operation, the time necessary for frozen that may require concurrent surgical re- section examination can be used by the sur- section. geon for inspection of the other parathyroid glands, also reducing surgeon anxiety. The choice of imaging technique The most common preoperative localisation Important points to know when proceeding methods are radionuclide scintigraphy and with parathyroid imaging ultrasound. As stated before, the two main • Imaging is not for diagnosis. The increase reasons for failed surgery are ectopic glands in plasma levels of calcium (normal value and undetected MGD (Levin and Clark 1989). 88–105 mg/l) and PTH (normal value 10–58 Because high-resolution ultrasound would, ng/l) establishes the diagnosis. even in skilled hands, fail to detect the major- ity of these cases, it is not optimal for preop- • Imaging does not identify normal parathy- erative imaging as a single technique. In the roid glands, which are too small (20–50 mg) study by Haber et al. (2002), ultrasound missed to be seen. six of eight ectopic glands and five of six cases of MGD. Ultrasound may, however, be useful • Imaging should detect abnormal para­ in combination with 99mTc-sestamibi imaging thyroid(s) and indicate the approximate size (Rubello et al. 2003). and the precise relationship to the thyroid (the level of the thyroid at which the para- 99mTc-sestamibi scanning is now considered thyroid lesion is seen on the anterior view; the most sensitive imaging technique in pa- and whether it is proximal to the thyroid or tients with pHPT (Giordano et al. 2001; Mullan deeper in the neck on the lateral or oblique 2004). Whatever the protocol used, 99mTc-ses- view or SPECT) (Fig. 1). tamibi scanning will usually meet the require- ment of detecting ectopic glands (all eight • Imaging should identify ectopic glands (add were detected in the study by Haber et al.). SPECT in cases of a mediastinal focus, and With regard to the recognition of MGD, how- ask for additional CT or MRI for confirmation ever, the protocol in use will determine the and anatomical landmarks) (Fig. 2). sensitivity. When 99mTc-sestamibi is used as a single tracer with planar imaging at two time • Imaging should be able to differentiate pa- points -- the “dual-phase” (or washout) method tients with a single adenoma from those – the sensitivity for primary hyperplasia is very with MGD (Fig. 3). low (Taillefer et al. 1992; Martin et al. 1996). Bet- ter results can be obtained by adding SPECT. • Imaging should identify thyroid nodules Subtraction scanning, using either 123I (Borley

 focussed parathyroid surgery is successfully is surgery parathyroid focussed who undergo bilateral surgery, those in whom patients with Compared 2005). Inabnet and scopic surgery under general anaesthesia (Lee endo video-assisted by or anaesthesia, local under possibly mini-incision, a through gery Focussed excision can be made by open sur cussed surgery instead of bilateral exploration. fo choose adenoma”,now may surgeon the “solitary a suggesting unequivocally focus, well-defined single a to points imaging tive routine bilateral exploration. When preopera of dogma the challenged have MGD detect and intraoperative monitoring of PTH to help operative adjuncts such as the gamma probe intra of availability the scanning, sestamibi of introduction the However,surgery. parathyroid in standard gold still the considered is exploration bilateral Conventional of minimallyinvasive parathyroid surgery Preoperative imaging era hasopenedanew etal. 2004). 1998;Mullan (Hindié time imaging the shortens and motion, tient pa to due images subtraction on artefacts simple answer to these difficulties. It prevents recordingof Simultaneous tracer. second this of images thyroid, to inject patient still for the time necessary to scan the culty with subtraction imaging is keeping the diffi One glands. hyperplastic for sensitivity to addition in or 2004) Mullan 2000; al. et Hindié 1996; al. et 99m Tc-pertechnetate (Rubello et al. 2003) al. et (Rubello Tc-pertechnetate 123 99m I and I 99m Tc-sestamibi, improves the improvesTc-sestamibi, Tc-sestamibi and to record 99m Tc-sestamibia be can 99m Tc------ relying solely on intraoperative measurements studies that is concern raises What debate. under still is MGD for PTH intraoperative of by a combination of both. The true sensitivity operative monitoring of PTH plasma levels, or appropriateimagingan protocol, intra by or preoperatively,through either MGD of cases distinguishing to committed is surgeon the surgery, minimal choosing when Therefore, MGD. unrecognised with those are surgery minimal of failure of risk specific at Patients 1999). easier thaninthepast(Utiger is surgery parathyroid that perception the to use a lower threshold for surgery is partly due now clinicians many that fact The activities. hypocalcaemia and an earlier return to normal course, less profound postoperative “transient” postoperative painful less a scar, cosmetic better a anaesthesia, local of possibility the time, operation shorter a enjoy completed tion study with high accuracy is mandatory to excellent interpretation of images. A localisa on also but surgeon experienced an on only not depends surgery parathyroid of success the operations, focussed of era new this In for MGD.high sensitivity detecting to select patients for focussed havesurgery a is thus important that imaging methods used higher rates of late recurrence is not known. It tine bilateral surgery. Whether this will lead to rou during observed generally is than lower fourtimes tothree is which 1996), al. et linari report a low percentage of MGD, only 3% (Mo Chapter 1:Applications ofparathyroid imaging - - - - EANM avoid conversion of the surgery to a bilateral With chronic stimulation, hyperplasia of para- exploration under general anaesthesia after thyroid glands accelerates and may develop minimal surgery has been started. It is impor- into autonomous adenomas. The extent of tant to avoid confusion with a thyroid nod- parathyroid growth then becomes a major ule, and precise anatomical description is also determinant of PTH hypersecretion. Second- important. With enlargement and increased ary hyperparathyroidism leads to renal bone density, superior parathyroid adenomas can disease, the development of soft tissue calci- become pendulous and descend posteriorly. fications, vascular calcifications and increased A lateral view (or an oblique view or SPECT) cardiovascular risk, among other complica- should indicate whether the adenoma is close tions. When medical therapy fails, surgery to the thyroid or deeper in the neck (tracheo- becomes necessary. Surgery can be either oesophageal groove or retro-oesophageal). subtotal parathyroidectomy, with resection This information is useful, because visualisa- of three glands and partial resection of the tion through the small incision is restricted. fourth gland, or total resection with grafting Moreover, the surgeon may choose a lateral of some parathyroid tissue into the soft tissues approach to excise this gland instead of an of the forearm in order to avoid permanent anterior approach. To achieve a high sensitiv- hypoparathyroidism. ity in detecting MGD with subtraction tech- niques, the degree of subtraction should be Preoperative imaging monitored carefully. Progressive incremental Surgery of secondary hyperparathyroidism subtraction with real-time display is a good requires routine bilateral identification of all way to choose the optimal level of subtraction parathyroid tissue. Moreover, early studies (residual 99mTc-sestamibi activity in the thyroid based on single-tracer 99mTc-sestamibi scan- area should not be lower than in surround- ning have reported a very low sensitivity ing neck tissues). Oversubtraction could easily of about 40–50% in detecting hyperplastic delete additional foci of activity and in some glands. Inefficiency of single-tracer techniques patients provide a false image suggestive of both in secondary hyperparathyroidism and a single adenoma. in primary hyperplasia is possibly due to more rapid washout of tracer from hyperplastic Secondary hyperparathyroidism glands than from parathyroid adenomas. For Secondary hyperparathyroidism is a common those reasons, preoperative imaging has not complication in patients with chronic renal yet gained wide acceptance among surgeons. failure. Hypocalcaemia, accumulation of phos- Dual-tracer subtraction imaging, planar or phate and a decrease in the active form of SPECT, provides substantial improvement in vitamin D lead to increased secretion of PTH. the rate of detection of hyperplastic glands in

10 before reoperation. landmarks anatomical of identification and technique (ultrasound or MRI) for confirmation radiological second a with matched be scan mend that lesions seen on the with primary hyperparathyroidism, we recom intervention is necessary for interpretation. As Knowledge of all details concerning the initial reoperation. before mandatory is Imaging not unusual, occurring in 10–30% of patients. Immediate failure and delayed recurrence are hyperparathyroidismor recurrent secondary findingsinpatientswithpersistent Imaging • • • What information canbeobtained? Perié etal. 2005) 1999; al. et (Hindié failure renal with patients (Hindié etal. 1999). (Hindié recurrence late or failure surgical prevent may it imaging, preoperative by provided ström et al. 1984). When this information is (Aker gland fifth supernumerary a have glands is four, some individuals (about 10%) Although the usual number of parathyroid imaging. preoperative without missed be would ectopia major with glands Parathyroid etal. 1999). (Hindié dissection thyroidof glands,reducingextent also the para aberrant of position the of ognition rec facilitate may map preoperative The 99m Tc-sestamibi - - - - 11 • • be emphasised: to need hyperparathyroidism secondary for Some aspects specific to patients reoperated was found at the predicted site. ofthe thyroid. At surgery, an adenoma of 1.9 g solitary adenoma located at the lower right pole Theanterior viewandthelateral viewshow a inapatient with primary hyperparathyroidism. taneousacquisition of Parathyroid subtraction scintigraphy, with simul Figure 1 vention (unpublisheddata). inter initial at missed parathyroid, fifth or and the other corresponding to an ectopic subtotally resected gland (or grafted tissue) the at disease recurrent to corresponding one activity, of foci two show to tients pa these in imaging for unusual not is It thyroid graft. obtained in patients who have had a para be should forearm the of views Specific Chapter 1:Applications ofparathyroid imaging 99m Tc-sestamibiand 123 - - - - I EANM Figure 2 This patient with a previous history of thyroid surgery (right lobectomy) was referred with a recent diagnosis of primary hyperparathyroidism. Ultrasound examination suggested the presence of a parathyroid adenoma at the side of previous thyroid lobectomy, which was a false-positive image. The large field of view 99mTc-sestamibi acquisition shows a mediastinal focus (arrow). The suspected ectopic parathyroid was confirmed by MRI (arrow). A mediastinal parathyroid adenoma of 0.59 g was resected.

Figure 3 Parathyroid 99mTc-sestamibi/123I subtraction scintigraphy in a patient with primary hyperpara- thyroidism. The computed subtraction images show two sites of preferential 99mTc-sestamibi uptake: one at the lower third of the left thyroid lobe and the second lateral to the lower pole of the right thyroid lobe. Two adenomas were excised: a left parathyroid adenoma weighing 2.3 g and a right adenoma weighing 0.07 g.

12 Therangeintravenouslyof administered radio 99m thyroid tissue than 99m tate administered is usually 185–370 MBq, becauseIf using the two radiopharmaceuticals is administered first. the administered radioactivity of tered activity is usually 75–150 MBq, depending roidonadenoma. When utilising images, and what remains is potentially a parathythensubtracted from the tioning thyroid parenchyma traps it. This image is used to delineate the thyroid gland because funcgamma energy of 140 keV. 99m 99m proportion to blood flow. normal parathyroid tissue and thyroid tissue in intravenously. administeredactivity is80 MBq and itis given (2%).keV135 The and(8%) keV 167 ducedat of 69–83 keV. In addition, gamma rays are pro mercury,energyofraysrangewhichhavean mainIts photo peak isdueto characteristic x- 201 201 scintigraphy are shown in Table 1. parathyroid for used commonly maceuticals fective dose and standard dose for radiophar energy,photopeak the of Details half-life, ef parathyroid scintigraphy usedforRadiopharmaceuticals Linda Tutty Radiopharmaceuticals Tl-chloride has a physicalh. half-life73.1aTl-chloride ofhas Tl-chloride Tl-chloride Tc-sestamibihigherhasa total activity thein Tc-pertechnetatehalf-lifehasaand a h 6of Tc-pertechnetate Tc-sestamibi 99m Tc-sestamibi, the amount of pertechne 201 Tl-chlorideistaken upby ab 201 Tl. 201 99m Tlor Tc-pertechnetate is 201 201 Tl,theadminis 99m Tl and which of Tc-sestamibi ------13 imaging agent in subtraction studies. The studies. subtraction in agent imaging with particularly used been has It keV. 159 of energy an with 123 123 is held there preferentially (Farley 2004). prominent in overactive parathyroid glands and in normal cardiac and thyroid cells; it is especially the mitochondria of many tissues but particularly mibi is within the mitochondria. It accumulates in 2005). The final cellular localisation of phaseandfunctional activity (Beggs andHain numerous factors, including perfusion, cell cycle (Farley 2004). exactmechanism uptakeof remains unknown idly than out of abnormal parathyroid tissue. The washesnormaloutof thyroid tissue morerap gland and functioning thyroid tissue, and usually MBq. This radiotracer localises in both parathyroidactivity 185-900is MBq;thetypical dose740is 11 11 is740MBq. ity 2004). The typical dose of administered activ Oates and (Smith characteristics imaging and sestamibi use as a parathyroid scintigraphy agent. for it license not do manufacturers Its 2004). is described in the literature (Smith and Oates 99m 99m 7.5 to 20MBq. from ranges orally, given dose, administered C-methionine C-methionine has a half-life of 20 min. It is It min. 20 of half-life a has C-methionine I has a half-life of 13 h and emits a photon a emits and h 13 of half-life a has I I-sodium iodide Tc-tetrofosminimagingparathyroid in use Tc-tetrofosmin 99m Tc-sestamibi uptake depends on 99m 99m Tc-tetrofosmin have similar Tc-tetrofosminhave Tc-sestamibithyroid- a as 99m Tc-sesta 99m Tc- - - - EANM cyclotron produced. Its uptake reflects amino method it is probable that each radiopharma- acid reflux into stimulated parathyroid tissue ceutical would provide the same diagnostic (Otto et al. 2004; Beggs and Hain 2005). Up- information (Kettle 2002). take in inflammatory conditions may pose a problem and should be considered when Subtraction agents interpreting images. The typical radioactivity Thyroid-specific imaging with 123I or 99mTc- dose ranges between 240 and 820 MBq, with pertechnetate may be employed using a sub- an average intravenous dose of 400 MBq. traction method to differentiate parathyroid from thyroid activity (Clark 2005). 18F-FDG 18F-FDG has a half-life of 110 min and is cy- The two main agents used for imaging the clotron produced. 18F-FDG allows glucose thyroid are 123I (sodium iodide) and 99mTc- metabolism to be assessed and evaluated pertechnetate. There is a slight preference for using PET. There is differential concentra- the use of 123I, as it is organified and therefore tion of FDG in abnormal parathyroid tissue provides a stable image. The pertechnetate and this difference is used to demonstrate washes out from the thyroid gland with time, the abnormal gland. FDG also accumulates and if there is some delay in imaging there in other malignant and benign tissues, and may be a reduction in the quality of the in inflamed or infected tissue; this potentially thyroid image (Kettle 2002). However, both limits its usefulness. The typical intravenous agents may be affected if the patient is taking dose is 400 MBq. thyroxine or anti-thyroid medications or has recently received iodine contrast agents. Radiopharmaceutical features Multiple radiopharmaceuticals have been Thyroid-specific radiopharmaceuticals may described for the detection of parathyroid le- aid delineation of the thyroid parenchyma if sions. Thallium, sestamibi and tetrofosmin are required after dual-phase imaging. This may the three most commonly used (Ahuja et al. be helpful as a second-line “visual subtraction” 2004). All these agents were originally devel- procedure when no parathyroid adenoma is oped for cardiac scanning. In the 1980s, 201Tl visible on dual-phase parathyroid imaging was the most commonly used agent, but it (Clark 2005). has a longer half-life and delivers a higher ra- diation dose to the patient (Kettle 2002). Con- Activities given for imaging the thyroid sequently, 201Tl is no longer commonly used, and parathyroid glands are as follows: 99mTc and most recent literature refers to the use of pertechnetate, 80 MBq; 123I, 40 MBq; 201Tl, 99mTc-sestamibi. However, for the subtraction 80 MBq; 99mTc-sestamibi, 900 MBq. If a 99mTc-

14 the choice of imaging agent depends on its on depends agent imaging of choice the Usually, characteristics. imaging comparable 99m results (Smith and Oates 2004). or mas can coexist and may retain 2005). However, thyroid adenomas and carcino delayedimagesOates2004;(SmithClarkand parathyroidvisibleonmore beshouldtissue target-to-backgroundabnormalthat so ratio gland.differentialThis washout improves the thyroidtheslowlyfrommoreclear may min glands(Smith andOates 2004). parathyroidabnormalbyretained usually is the thyroid with a half-life of about 30 min but SPECT imaging. thyroid gland possible on planar as well as early therelation toadenomain correlation the of parathyroidin adenomas.aswell makes This thyroidas glandthetracersTheselocalise in faster rate of washout from the thyroid gland. andtheparathyroid similaraat rate, therea is rofosmin are taken up by both the thyroid gland the fact that while scintigraphy.The washout technique relies on monlyused agents for dual-phase parathyroid 99m agentsDual-phase to 18.3mSv.this rises bined study is 11.6 mSv. If com the for dose radiation the then used is pertechnetate/ Tc-sestamibiand cssaii and Tc-sestamibi 99m Tc-tetrofosmin,resulting falsepositivein 99m 99m 99m Tc-sestamibi is released from Tc-sestamibi combination Tc-sestamibi 99m Tc-sestamibi and 99m Tc-tetrofosminare com cttoomn have Tc-tetrofosmin 123 I and 99m 99m 201 Tc-sestamibi Tc-tetrofos Tl are used, 99m Tc-tet - - - - - 15 nine PET holds more promise than FDG PET im et al. 2004). It has been shown that parathyroid glands (Beggs and Hain 2005; Otto results when using FDG as a tracer to image the Initial studies with PET have shown conflicting scribed (Otto et al. 2004; Beggs and Hain 2005). nine PET for parathyroid imaging has been de emissiontomographyand (PET) ofUse imaging agents PET and Oates 2004). (Smith mass palpable a with patients those ing thyroid disease, after thyroid surgery or in underly confounding other or goitres with patients in essential, even or helpful, be may junctive thyroid-selective imaging ( The dual-phase subtraction method with ad medicine radiologist. availability and the experience of the nuclear scintigraphy. parathyroid for used radiopharmaceuticals to reactions and side-effects shows 2 Table radiopharmaceuticals Adverse to reactions hyperparathyroidism (Beggs and Hain 2005). has been performed but has failed to correct the ingtosurgery, orinpatients inwhom surgery failed to localise the adenoma before proceed in which conventional imaging techniques have valuein cases of primary hyperparathyroidism Hain2005). aging of the parathyroid localisation (Beggs and 18 F-fluorodeoxyglucose (FDG) positron 11 C-methioninescanningPET ofis Chapter 2:Radiopharmaceuticals 11 11 C- methioC- 99m C-methio Tc or 123 I) ------EANM Table 1 Radiopharmaceuticals used for parathyroid scintigraphy 201Tl- 99mTc 99mTc 11C 18F chloride sestamibi tetrofosmin methionine fluorodeoxy- glucose Photo peak 69-80 (98% 140 140 511 511 energy abundance) (keV) 135 (2%) 167 (8%) Half-life 73.1 hours 6 hours 6 hours 20 min 110 min

Cyclotron Always Always Cyclotron Cyclotron product available available produced produced to be (24-month (6-month ordered shelf life at shelf life at ready for room 2-8°C use temperature) Effective 18 11 9 2 10 dose adult (mSv) Standard 80 900 900 400 400 dose*(MBq)

*Allowable upper limits of radiotracers may differ from country to country. Please refer to the Summary of Product Characteristics in each European country. Doses given here are quoted from ARSC, December 1998.

16 Nucl Med 1996;37:185–192,1064–1067) Nucl Med J in printed (as scintigraphy parathyroid for used radiopharmaceuticals to reactions Adverse Table 2 201 Radiopharmaceutical 18 99m 123 99m 99m F-FDG TI-chloride I-Sodium iodide I-Sodium Tc-tetrofosmin Tc-sestamibi Tc-pertechnetate 17 pruritis, hypotension Fever, flushing, diffuserash, erythema, reactions Side-effects, Angina, hypertension, torsadesAngina, de hypertension, headache, tachypnea, parosmia tachycardia, syncopeorfaintnessand or heaviness, reaction, respiratory chest pain, tightness pruritus, hives/urticaria, Nausea, vomiting, diffuserash, tingling pruritis, seizures, headache, metallictaste, flushing, diffuserash, Nausea, erythema, anaphylaxis dizziness, headache, vertigo, diaphoresis, tightness orheaviness, hypertension, chestpain, pruritis, hives/urticaria, Chills, nausea,vomiting, diffuserash, None mouth, unusualodour, mildleucocytosis dyspnoea, metallictaste, of burning cutaneous allergy, hypotension, vomiting, abdominaldiscomfort, disease); heart because ofunderlying pointes (thesethree probably occurred Chapter 2:Radiopharmaceuticals

EANM Imaging equipment – preparation and use José Pires Jorge and Regis Lecoultre

Quality control procedures that must be Checking the peaking is needed to ascertain satisfactorily performed before imaging that: After acceptance testing, a QC protocol must be set up in each department and followed • The camera automatic peaking circuitry is in accordance with national guidelines. The working properly following routine quality control test schedule is typical: • The shape of the spectrum is correct a) Daily energy peaking • The energy peak appears at the correct energy b) Daily flood uniformity tests • There is no accidental contamination of the c) Daily gamma camera sensitivity measure- gamma camera ment It is recommended that the spectra obtained d) Weekly linearity and resolution assess- during peaking tests are recorded. ment Daily flood uniformity tests e) Weekly centre-of-rotation calibration After a successful peaking test it is recom- mended that a uniformity test is performed A routine quality control programme for a on a daily basis. Flood fields are acquired and SPECT gamma camera includes quality control evaluation of camera uniformity can be made procedures appropriate to planar scintillation on a visual assessment. Quantitative param- cameras (a–d) and specific SPECT quality con- eters should also be computed regularly and trols (e). Further, more complex tests should be recorded in order both to demonstrate sud- undertaken on a less frequent basis. den variations from normal and to alert the technologist to progressive deterioration in Energy peaking the equipment. On cameras that have inter- This quality control procedure consists in changeable uniformity correction maps, it “peaking” the gamma camera for relevant is vital that one is used that is for the correct energies prior to obtaining flood images. It ­nuclide, accurate and up to date. is mandatory that the energy peaking is un- dertaken on a daily basis and for each radio- Daily gamma camera sensitivity nuclide used. measurement A practical means of measuring sensitivity is

18 resolution and taking into account that in that account into taking and resolution some of expense the at possibly maximised, resolution. The number of counts needs to be spatial the and images projection the of tent con noise statistical the influence will This activity. tracer the by determined mainly is study given a for collimator a of choice The Collimator should notexceed 0.5pixels. viations between the actual and fitted curves maximum count locations to a sine wave. De the fit to used is and projections the from rotation of the camera. A sinogram is formed of centre mechanical the from offset slightly placed source point a of acquisition graphic tomo a of reconstruction the from made is rotation of centre the of calibration The respond automatically. cor not do these as reconstruction, for used matrix the of centre the and camera the of mines the offset between the axis of rotation deter measurement rotation of centre The Centre ofrotation calibration phantoms. weekly. This may be done using transmission assessed be should resolution and Linearity andresolution assessment Weekly linearity day to another. not vary by more than a few percent from one flood field using known the activity. It should acquirethe to needed recordingbytime the - - - - - 19 Chapter equipment 3:Imaging -preparation anduse furthermore, the resolution of a high-resolu a of resolution the furthermore, count rate is no longer a major limitation, and 99m With recommended. is collimator purpose general- low-energy a traditionally so dose; limited consequent the and isotope the of half-life long the to owing reduced greatly using When tial resolution. better count sensitivity but with a loss of spa a gives hole larger a Conversely,sensitivity. obtained, but at the expense of a lower count resolution spatial the better the length, hole length and width of the holes. The longer the relative the to respect with vary Collimators roid) mustbesignificant. any between activity tracer in difference the imaging parathyroid The SPECT images (or projections from the from projections (or images SPECT The Matrix andzoom factor view. per time the and angles of number the size, matrix the as such resolution, spatial optimal aspects play an important role in determining should be borne in mind that other technical Although the choice of collimator is crucial, it sensitivity.lower the despite imaging, SPECT for recommended currently is collimator high-resolution a Thus collimator. purpose general- a of that does than source the from distance with less decreases collimator tion Tc-pertechnetate and 99m Tc-labelled agent (thyroid and parathy 201 l te vial cut are counts available the Tl, 99m TcO 99m 4 (thyroid only) and only) (thyroid Tc-labelled agents, - - - EANM angles round the patient) create multiple raw a factor of 4. 128×128 matrices produce ap- data sets containing the representation of the proximately three times more noise on the data in one projection. Each of these is stored image after reconstruction than do 64 x 64 in the computer in order to process them later matrices (Garcia et al. 1990). on and extract the information. The planar images (or static projections) do Matrix not have the reconstruction problem and can Each projection is collected into a matrix. be acquired over longer times so a 256× 256 These are characterised by the number of matrix is commonly used. picture elements or pixels. Pixels are square and organised typically in arrays of 64×64, Zoom factor 128×128 or 256×256. The pixel size is dependent on the camera field of view (FOV). When a zoom factor of In fact, the choice of matrix is dependent on 1.0 is used, the pixel size (mm) is the useful two factors: FOV (UFOV, mm) divided by the number of pixels in one line. When a zoom factor is used, a) The resolution: The choice should not de- the number of pixels per line should first be grade the intrinsic resolution of the object. The multiplied by this factor before dividing it into commonly accepted rule for SPECT (Groch the FOV. and Erwin 2000) is that the pixel size should be one-third of the full-width at half-maximum Example: (FWHM) resolution of the organ, which will Acquisition with matrix 128, zoom 1.0 and depend on its distance from the camera face. UFOV 400 mm. Pixel size: 400/128=3.125 mm. The spatial resolution of a SPECT system is of the order of 18–25 mm at the centre of rota- The same acquisition with a zoom factor of 1.5. tion (De Puey et al. 2001). Thus a pixel size of Pixel size: 400/(1.5×128)=2.08 mm. 6-8 mm is sufficient, which, for a typical large field of view camera, leads to a matrix size of It is important to check this parameter be- 64×64. fore the acquisition, as it is very often used in parathyroid imaging, especially if a subtraction b) The noise: This is caused by the statistical technique is used. fluctuations of radiation decay. The lower the total counts, the more noise is present and, if Preferred orbit the matrix size is doubled (128 instead of 64), Either circular or elliptical orbits can be used the number of counts per pixel is reduced by in SPECT imaging (Fig. 1). A circular orbit (Fig.

20 and closely follow the contours of the body the of contours the follow closely and learn to camera the allow that Programmes using filteredconstructing backprojection. re when areas photopenic small simulating artefacts generate may This orbit. circular a with than orbit elliptical an with significantly more varies detector the to organ the from distance the angles.all at body Nevertheless, the to closer passes camera the as improved With an elliptical orbit, spatial resolution will be images. will reduce the resolution of the reconstructed projections.these resolutionin spatial in This the body at some angles, causing a reduction With a circular orbit, the camera is distant from Figure 1bellipticalorbit Figure 1acircular orbit the bodyoutlinemore closely. follow 1b) (Fig. orbits Elliptical angles. all for of rotation to the centre of the camera surface 1a) is defined by a fixed distance from the axis Figure 1a Figure 1b

- 21 Chapter equipment 3:Imaging -preparation anduse tomical locations makes SPECT a useful tool useful a SPECT makes locations tomical and mediastinum. The oftheseana diversity neck the in low or high thyroid,fromas such distant regions anatomical in or thyroid, the within or alongside,beside locations: diverse in found be can adenomas ever,parathyroid How adenoma. parathyroid single a usually production, hormone parathyroid of site the identify to is procedures imaging roid parathy medicine nuclear of goal main The reconstruction: someconsiderations Filtered image backprojection or contoured orbit. tefacts that may be generated by an elliptical orbit has to be offset against the potential ar circular a with resolution spatial of loss The the databefore reconstruction. at the expense of computing power to modify are available and improve resolution, although mation. It mation. should It produce results that lead to infor losing or artefacts creating data, input the of components the altering significantly without information, image enhances that A filter in SPECT is a data processing algorithm et al. 1998). jection for reconstruction is crucial (Pires Jorge pro back filtered using when filter optimum an of choice The activity. thyroid normal to close often uptake increased with structures Furthermore, parathyroid adenomas are small in parathyroid imaging. ------EANM a correct diagnosis. Incorrect or over-filtering The input data plotted in the image frequen- may produce adverse effects by reducing ei- cy-amplitude domain present three com- ther resolution or contrast, or by increasing ponents that are partially superposed: the noise. low-frequency background, useful or target data and the high-frequency noise. Here back- A filter in SPECT, being a processing algorithm, ground does not mean surrounding natural operates in the frequency-amplitude domain, radiation or surrounding non-tissue activity which is obtained from the spatial domain by but rather the low-frequency waves gener- the Fourier transform. In the spatial domain, ated by the reconstruction process, such as the image data obtained can be expressed by the well-known “star artefact” that appears in profiles of any matrix row or column show- an unfiltered back projection. The high-fre- ing the activity distribution (counts) as a func- quency noise is related to background and tion of distance (pixel location). The Fourier scatter radiation or statistical count fluctua- method assumes that this profile is the sum tions during SPECT acquisition, which may of several sine and cosine functions of differ- induce image distortions. ent amplitudes and frequencies. The Fourier transform of the activity distribution of a given Usually SPECT filtered back projection couples profile is a function in which the amplitude of a ramp filter with an additional filtering (e.g. the sine or cosine functions is plotted against Hann, Hamming, Parzen). The ramp filter is the corresponding frequency of each. This rep- so called as its shape looks like a ramp and resentation is also called the image frequency- it will eliminate an important portion of the amplitude domain. unwanted low-frequency background. How- ever, the ramp filter amplifies the contribution In input data, the highest frequency that of the high-frequency noise to the image. This can be measured is named the “Nyquist fre- is why it is recommended that an additional quency”, which is determined by the matrix filter be coupled with the ramp filter in order size as well by the scintillation detector size to smooth an image where some details could and is expressed by the formula: fn=1/(2×d) appear very noisy. The degree of smoothing where fn is the Nyquist frequency and d is the for each additional filter is under the control acquisition pixel size. For example, when using of the user, as s/he has to decide the “cut- a 64×64 matrix with a 41-cm gamma camera off” frequency at which the filter will be ap- UFOV, the pixel size (d) is 0.64 cm. Therefore plied. The cut-off frequency is the frequency the Nyquist frequency is 0.78. This means that value that defines the maximum frequency any input data where the frequency is higher acceptable (which may contain useful data) than 0.78 cannot be measured. while ignoring the higher frequency noise.

22 ated because ofthelow imagesmoothing. toler be to have will frequency) (high noise target and data, conserve although cy) some background image components (low frequen the eliminate order to in applied be will filter type high-pass A frequency. Nyquist the to type filter with a cut-off frequency value close ity, the optimum choice of filter is a“high-pass” spots, frequently within normal thyroid activ As parathyroid adenomas appear as small hot frequency.Nyquist the is filter additional given a for frequency cut-offthe of value maximum the Obviously - - - 23 Chapter equipment 3:Imaging -preparation anduse

EANM Patient preparation Audrey Taylor and Nish Fernando

Patient identification To minimise the risk of a misadministration: A minimum of TWO corroborative details should be requested and confirmed as cor- • Establish the patient’s full name and other rect. relevant details prior to administration of any drug or radiopharmaceutical. The following information should be checked with the patient/parent/guardian/escort • Corroborate the data with information pro- where appropriate: vided on the diagnostic test referral. • Referring clinician/GP/hospital If the information on the referral form does not match the information obtained by the • Any relevant clinical details identification process, then the radiopharma- ceutical/drug should not be administered to • Confirmation that the patient has complied the patient. This should be explained to the with the dietary and drug restrictions patient and clarification sought as soon as possible by contacting the referral source. • Confirmation that the results of correlative imaging (e.g. echocardiography, angiogra- The patient/parent/guardian/escort should phy, etc.) are available prior to the study, and be asked for the following information, which noting of any recent interventions should then be checked against the request form and ward wristband in the case of an If in doubt, do not administer the radiophar- in-patient: maceutical or drug and seek clarification.

• Full name (check any spellings as appropri- Specific patient groups ate, e.g. Steven vs Stephen) This is a guide only. Patients who are unable to identify themselves for any of a variety of rea- • Date of birth sons should wear a wrist identification band.

• Address • Hearing difficulties: Use written questions and ask the patient to supply the information • If there are any known allergies or previous verbally or to write their responses down. reactions to any drug, radiopharmaceutical, iodine-based contrast media or products • Speech difficulties: Ask the patient to write such as micropore or Band-Aids down their name, date of birth and address and other relevant details.

24 given withregard to eating, medicationetc. as to ensure that the appropriate guidance is contact the department if they are diabetic so chosen in advance. They should be advised to be can drugs stressing that so status asthma medications, approximate height, weight and of list a in send to required be can Patients details.evant rel the confirming evidence written provide to as so sign to them for advisable is it etc., formation re the patient’s name, date of birth in provides interpreter or friend relative, a If • • • to positivelythepatient’s confirm ID. patient the accompanying person the ask patient’sID. out-patient,an is patient the If the confirm positively to patient the after wristband is attached, ask the nurse looking no If birth. of date and name correct the for wristband ID patient’s the check tient, Confused patient: If the patient is an in-pa thepatient’sconfirm ID. nurse looking after the patient to positively of birth. If no wristband is attached, ask the ID wristband for the correct name and date patient’s the Check patient: Unconscious is available. interpreter an or skills language propriate ap the with relative or staff of member a when rebooked be should study the then person is unable to interpret the questions, accompanying an If difficulties: Language - - - - 25 any concerns. discuss to opportunity an patient the gives and test the of reminder a as acts it ment, appoint to prior phoned are patients the If for scan,theneedto remain stilletc. taken used, time stress agents of side-effects and contraindications risks, including, given, A full explanation of the procedure should be Chapter 4:Patient preparation - EANM Pregnancy Women of childbearing potential should have their pregnancy status checked using a form such as the example below:

QUESTIONNAIRE FOR ALL FEMALE PATIENTS OF CHILD BEARING AGE (12 – 55 YEARS) We are legally obliged under The Ionising Radiation (Medical Exposure) Regulations 2000 to ask females of child bearing age who are having a nuclear medicine procedure whether there is any chance they may be pregnant or breastfeeding. Prior to your test, please answer the following questions in order for us to comply with these regulations:

PATIENT NAME ...... D.O.B 1. Have you started your periods? (please tick appropriate box)

Y ❐ What is the date of your last period ......

N ❐ Please sign below and we can then proceed with your test

OR Have you finished your periods / had a hysterectomy (please tick appropriate box)

Y ❐ Please sign below and we can then proceed with your test

N ❐ What is the date of your last period

2. Is there any chance you may be pregnant (please tick appropriate box)

Y ❐ We will need to discuss your test with you before we proceed

Not sure ❐ We will need to discuss your test with you before we proceed

N ❐ Please sign below and we can then proceed with your test

3. Are you breastfeeding? (please tick appropriate box)

Y ❐ We will need to discuss your test with you before we proceed

N ❐ Please sign below and we can then proceed with your test

26 (e.g. nurse) escort pregnant not is person accompanying any that check should radiopharmaceutical the dren. In addition, the operator administering chil and persons pregnant with contact ing ceutical should advise the patient on minimis The operator administering the radiopharma Signed: baby. developing a damage could radiation ionising that aware am I that and breastfeeding or pregnant not am I that confirm and above questions the understood and read have I THIS FORM WILL BECHECKED/DISCUSSEDPRIOR TO THE START OF THE TEST Parent Signed: pregnant orbreastfeeding I have read and understood the question above and confirm that the patient named is not (Patient) ❐ ______

Guardian For allpatients under16years ofage ❐

(please tickappropriate box) - - - 27 • • Parathyroid patient preparation imaging procedure using iodine contrast iodine using procedure imaging any had has patient the whether Establish to imaging. any thyroid medication for 4–6 weeks prior referring clinician, the patient should be off the from guidance under and possible, If Date: Date:

______Chapter 4:Patient preparation

EANM within the last 6 weeks (CT with contrast, also whether he or she is claustrophobic. IVU etc). Allow a period of 6 weeks between Consider another imaging modality if the these procedures and thyroid imaging. patient cannot lie still for the duration of the study owing to discomfort or anxiety. • Iodine-containing medications may have to be withdrawn, and the referring clinician’s • Although 123I sodium iodide contains little advice should be sought. These medica- carrier-free iodide, it is important to ask tions include: propylthiouracil, mepro- the patient about any adverse reactions bamate, phenylbutazone, sulphonamides, to iodide in the form of contrast media or corticosteroids, ACTH, perchlorate, anti- medication. If positive, seek the advice of histamines, enterovioform, iodides, Lugol’s the lead clinician. solution, vitamin preparations, iodine oint- ments and amiodarone.

• Before any pharmaceuticals are ordered, check whether the patient has had a total thyroidectomy. If this is the case, then the subtraction technique should not be car- ried out and consideration should be given to undertaking a dual-phase 99mTc-sestamibi study.

• Ask the patient whether he or she has any thyroid disorders such as thyrotoxicosis, hypothyroidism, thyroid nodules or thy- roid goitre. These conditions can increase instances of false-positive 99mTc-sestamibi uptake and also affect 123I sodium iodide uptake. In the case of hypothyroidism, do not carry out the subtraction technique and consider undertaking a dual-phase 99mTc- sestamibi study.

• Ask the patient whether he or she is able to lie supine for the duration of the study and

28 • • subtraction 123 scope ofthisbooklet. the beyond is but 2005) al. et (Gayed tection de of sensitivity the increase to technique suitable a as suggested been has SPECT/CT oftheireffects. with knowledge the choices so that adaptations can be made amples only. Explanations have been given for are described, including SPECT imaging, as ex One subtraction and one washout technique obviates problems ofimageregistration. downscatter, by affected although imaging, simultaneous course, Of first. use to nuclide which considering when nuclide energy higher the from downscatter and uptake of images, consideration must be given to timing ond nuclide being injected after the first set of images are acquired sequentially with the sec where studies dual-isotope For used. tocols There are many variations in the imaging pro FernandoNish andSueHuggett protocolsImaging I sodiumiodide/ venflon. Also, the patient has more freedom butterfly needle than around the plastic of a as veins more frequently collapse around a needle butterfly a than convenient more is hand the of back the or arm patient’s the in vein a into system tap three-way a Ensure good venous access. A venflon with of keeping still during the acquisition. patient.particular,In stress the importance Give a full explanation of the procedure to the 99m Tc-sestamibi - - - - 29 • • • • • pillow placed underneath the knees can knees the underneath placed pillow A still. keep to need the understands and and neck. Ensure the patient is comfortable head the immobilise to strap a and bags sand Use pillow. a on shoulders his/her Ensure the neck is extended by positioning tient supine on the gamma camera couch. post min 40 At ofdelay. theperiod will protect itduring the arm or hand where the venflon is sited flush of 10 ml. Wrapping a bandage around Inject of movement ifavenflon isinserted. ai aqiiin with acquisition namic dy dual-isotope a using injection iodide acquisition at 60 min post Start the venflon if the vein has collapsed. flon by flushing through with saline.Re-site onto an arm rest. Ensure patency of the ven thatvenflonthehas three-wayand system cluded in the image. Place the patient’s arm tained, allowing any ectopic tissue to be in of the thyroid and mediastinum can be ob Position the patient so that an anterior image reduce backdiscomfort. At 50 min post still.of keeping importance the stress Again, procedure. the understands she or he whether tient pa the Ask bladder. the empty to tient 123 I sodium iodide followed by a saline 123 I injection, position the pa 123 I injection, ask the pa the ask injection, I non-overlapping non-overlapping 123 I sodium ------EANM windows for 99mTc (-10% to +5% about Processing the peak at 140 keV) and 123I (-5% to +10% In order to detect the increased uptake of about the 159-keV peak). 99mTc-sestamibi in the parathyroid tissue it is necessary to subtract the 123I image from the • Acquire 2-min frames for 20 min using a 99mTc-sestamibi image. zoom of 4.0 and a matrix of 128×128. A dynamic acquisition is preferable to a static The precise computer protocol will vary from one as movement correction, provided it is centre to centre and even from camera system in the x- or y-direction, can be applied to the to camera system. However, all protocols will images. The large zoom is chosen in order follow the same basic steps. to increase spatial resolution. However, this will increase noise in the image and so the Movement correction acquisition must be of sufficient duration As the images have been acquired simultane- to compensate for this. ously, there will be no need to match the posi- tions by shifting either image, but the images • Pure iodide images may be acquired for 10 should be checked for movement and any min. As well as being critical for processing, correction algorithms applied before com- these pure iodide images can be beneficial mencing. This can be as simple as checking in reducing false-positive cases due to thy- all the frames and rejecting any with blurring roid disease. before the frames are summed. This will not help if the patient has moved to a different • Without any patient movement, inject 99mTc- position rather than having coughed or swal- sestamibi followed by a 10-ml saline flush, lowed deeply and returned to the original between the 11th and 12th minute and position. continue the acquisition for 30 min. If overall movement has occurred, the situa- • As a large zoom has been used, it is advis- tion may be rescued if the subsequent frames able at the end of the dynamic acquisition can be shifted by reference to some standard to carry out an unzoomed image to include point (sometimes the hottest pixel) or even the salivary glands and the heart. This will by eye. ensure the detection of any ectopic para- thyroid glands, which can occur in the re- The subtraction gion of the unzoomed image. Acquire this Both sets of frames (corrected if necessary) image on the same dual-isotope settings for are summed to make one 99mTc and one 123I 300 s onto a matrix of 256×256. image.

30 method. dual-isotope dual-phase the either to addition useful a be can SPECT delayed and early both Acquiring calisation. lo anatomical precise more and sensitivity increased gives imaging SPECT Additional imaging SPECT the operator to choose the best result. there are usually two or three options offered andfor the results displayed as a new image. Again, imageis then subtracted from the from the ratio of these two values. This adjusted the pared against the counts in the same region on edges. Thecounts in this region are then com the count contour line which best represents its 123 interestof around thenormal thyroid theon moreAautomated system willdrawregion a being chosenby eye. tissue thyroid the eliminating for result best 99m from areturn the images in these subtracted and values, original its of 70% and 60% 50%, 40%, 30%, example, for to, subtracted be to image the reduces technique simplest The age are reduced by this factor, pixel by pixel. used so that the counts in the subtraction im image before subtraction and a scaling factor is 123 There will be more counts in the thyroid on the I imageIallowingby theoperator chooseto I image, so it must be matchedthebetomust itimage, soI Tc-sestamibi image, that which gives the gives which that image,Tc-sestamibi 99m Tc image. The scaling factor is calculated 99m 123 cssaii ehd r the or method Tc-sestamibi I/ 99m Tc-sestamibi subtraction subtraction Tc-sestamibi 99m Tcimage 99m Tc - - - 31 • • • • • • • • • both headsare used for theacquisition. useful and more counts will be collected as headed camera, a 90 If the acquisition is carried out on a double- the after should Early SPECT be acquired 10–30 min A 64×64 matrix is sufficient for the expected be enoughcoverage ofthemediastinum. resolution than no zoom, and there should Using a zoom of 2 will ensure better spatial num to locate any glands there. ectopic allows adequate coverage of the mediasti It should be ensured that the zoom chosen acquisition. the during closer move will camera the if warned be should patient the though al available, if used be can Contouring tion andstop at90 270 at head camera the with start should Acquisition the bodysurface. to close so structures with problem a not is attenuation and interest of area the to An 180 123 both for peaked is camera The ataround 3hpostinjection. layed SPECT I asbefore. o acquisition optimises the time close 99m o Tc-sestamibi injection and de and Tc-sestamibi injection ; proceed in a clockwise rota clockwise a in proceed ; Chapter protocols 5:Imaging o . o L-Mode SPECT will be 99m Tc and Tc - - - - EANM resolution and will optimise counts per pixel 99mTc-sestamibi washout technique and hence reduce noise. If 99mTc-sestamibi is used alone, the two sets of images (early and delayed) are inspected • 30× 60-s frames is manageable for the patient visually. and will maximise counts in the image. 740 MBq 99mTc-sestamibi is injected using the • For delayed SPECT, increasing the time same protocols for patient preparation, i.e. per projection to 90 s will restore the total ID and LMP checks/explanation to patient as counts. before and imaging typically at 10 min and 2–3 h Processing • The data may be reconstructed using the • The camera is peaked for technetium and methods of filtered back projection or itera- a low-energy high-resolution collimator tive reconstruction. Streak artefacts may be can be used as images can be taken for seen in data reconstructed by filtered back a sufficient time to avoid statistical noise projection and these will not occur for the problems and pinhole collimators are used iterative method. in some centres. Zoom can be used but remember the possibility of ectopic tissue. • The raw data can be viewed as a rotating image and the limits for the region to be • Neck and mediastinum views are taken with reconstructed chosen. patient positioning as before. Again, a single view of 600 s counts can be taken or a series • The region should extend from the parotid of 10×60-s frames acquired so that move- glands to the mediastinum to locate any ment artefacts can be corrected. ectopic tissue. • The same parameters and positioning must • The reconstruction programme with cho- be used for the 10-min and late views sen filters is initiated. • Right and left anterior oblique views can be • Once the reconstruction is completed, the obtained if required. images are viewed in the transverse, coronal and sagittal planes. • SPECT can be used in this case also.

• Datasets can be viewed as volumetric dis- All films should be correctly annotated with L, plays as well as tomographic slices. R and anatomical markers and labelled.

32 dose –740–925MBq. ‘high’ a uses which nique, tech MIRS traditional the with compared – low very a of injection the on based is centre our in oped devel technique MIRS the Moreover, nique. mainly on technical aspects of the MIRS tech enlarged gland. The present chapter focusses the precisely locate to (b) and solitary tively effec is adenoma parathyroid the whether preoperative imaging in order (a) to establish accurate requires always parathyroidectomy course, in contrast to BNE, minimally invasive cm skin incision have been widely adopted. Of 1–2 small a via parathyroidadenoma solitary thyroidectomy consisting in the removal of a para invasive minimally to approaches New (QPTH) andgammaprobes.hormone operative measurements of quick parathyroid microsurgery instruments, endoscopes, intra- of availability the with practice surgical into introduced improvements technical the (b) and 85%), least (at patients of majority the in pHPT is due to a single parathyroid adenoma that reasons:consciousness main the (a) two (MIRS). This development can be attributed to surgery radio-guided or surgery endoscopic of minimally invasive parathyroidectomy using during the past decade, with the development centres surgical many in significantly altered er, surgical approaches to pHPT patients have primary hyperparathyroidism Howev (pHPT). the ‘goldstandard’with patients in approach Bilateral neck exploration (BNE) still represents Rubello Domenico parathyroid adenomas forTechnical surgery ofprobe-guided aspects 99m Tc-sestamibi dose – 37 MBq MBq 37 Tc-sestamibi– dose 99m Tc-sestamibi ------

33 patient scheduled for MIRS while Fig. 2 shows a shows 1 Figure surgery. during results tive posi false cause can adenoma, parathyroid a mimicking by which, nodules, thyroid avid of presence the is exclusion tients can be offered MIRS. The main reason for adopted, approximately 60–70% of pHPT pa are criteria inclusion these When MIRS. to contraindication a not is surgery parathyroid thyroidor previousnote, Of neck. the to tion irradia of history no (e) and neoplasia; crine (d) no history of familial HPT or multiple endo and high-resolution (10 MHz) neck ultrasound; thyroid nodules at thyroid adenoma; (c) absence of concomitant (b) intense adenoma; parathyroid solitary a of tigraphy followed: (a) evidence at be to need criteria inclusion strict BNE), ing perform when (unlike MIRS planning When criteria for offeringSelection MIRS (SPECT) examination is obtained to investi to obtained is examination (SPECT) mibi positive and US negative) a tomographic in cases with discrepant findings ( while performed, is imaging further no tive), and ultrasound results (both positive or nega concordant with patients In 2000). al. et Rubello 2003; al. et Norman Mariani 1999; and Costello 1997; Chheda and (Norman ultrasound neck and scintigraphy single-session include dures protocol,our In preoperative imaging proce Preoperative imaging protocol a patientexcluded from MIRS. 99m Tc-sestamibi uptake in the para 99m Tc-sestamibi scintigraphy 99m Tc-sestamibi scin 99m 99m 99m Tc-sestamibi- Tc-sestamibi Tc-sestamibi 99m Tc-sesta ------EANM gate a possible ectopic or deep position of the the surgeon to become more skilled in the parathyroid adenoma. SPECT is obtained just use of the probe. after the completion of planar 99mTc-sestamibi scintigraphy, thus using the same radiotracer The probe is usually handled by the surgeon, dose; in this way, 99mTc-sestamibi re-injection is who should measure radioactivity in differ- not necessary, thus avoiding additional radia- ent regions of the thyroid bed and neck in an tion exposure to the patient and personnel. attempt to localise the site with the highest In other centres, preoperative 99mTc-sestamibi count rate before commencing the operation. scintigraphy alone is considered a sufficient This site is likely to correspond to the parathy- tool for the planning of MIRS. roid adenoma. Then, during the operation, the surgeon should measure the relative activity Intra-operative MIRS protocol levels in the parathyroid adenoma, thyroid Table 1 shows the steps in the MIRS protocol bed and background. Moreover, a check of used in our centre. the empty parathyroid bed after removal of the parathyroid adenoma is a very useful A collimated gamma probe is recommended parameter to verify the completeness of re- with an external diameter of 11–14 mm. A moval of hyperfunctioning parathyroid tissue. non-collimated probe, which can be used for Ex vivo measurement of any removed surgical sentinel lymph node biopsy, is not ideal for specimen should be done to verify the total parathyroid surgery owing to the relative com- clearance of the parathyroid adenoma. The ponent of diffuse and scatter radioactivity de- calculation of tissue ratios – parathyroid to riving from the anatomical structures located background (P/B) ratio, thyroid to background near to the parathyroid glands, mainly related (T/B) ratio, parathyroid to thyroid (P/T) ratio to the thyroid gland. Probes utilising either a and the empty parathyroid bed to background NaI scintillation detector or a semiconductor (empty-P/B) ratio – can be useful in evaluating detector have proved adequate for MIRS. the efficacy of MIRS. The tissue ratios obtained in a large series of 355 pHPT patients operated A learning curve of at least 20–30 MIRS op- on in our centre are reported in Table 2. erations is recommended for an endocrine surgeon. During these, the presence in the Attention has to be given to avoidance of operating theatre of a nuclear medicine phy- intra-operative false negative results due to sician is usually considered mandatory. In 99mTc-sestamibi-avid thyroid nodules and to the opinion of the writer, the presence of a stagnation of the radiotracer within vascular nuclear medicine technician, with expertise structures of the neck and thoracic inlet: in this in probe utilisation, is very useful in helping regard, the careful acquisition and evaluation

34 dose of dose MBq 740–925 or 20–25 a with injected is patient The approach. surgery and imaging single-day a of consists It 1997. in Norman by developed was protocol MIRS first The dose different-day protocol protocol versus thelow high The single-day cessful parathyroidectomy. suc of indicative considered usually is value pre-excision baseline the with comparison in removal adenoma parathyroid after min 10 levels PTH in more or 50% of fall a QPTH, using When MIRS. of purpose the for ficient other authors judge the use of the probe suf some while hyperplasia, glandular unknown possible discover to order in authors some QPTH measurement is also recommended by The performance of additional intra-operative a majorrole. play should technician medicine nuclear the which in step important an is This months. 3–6 every performed be should and earity lin count and resolution spatial sensitivity, include should probe the of controls Quality photo peak of per second. An energy window of 10% of the counts in be should measurements these All Technical factors intheopinionofauthor). (mandatory helpful very is scintigraphy preoperative of 99m Tc-sestamibi,obtained are images 99m Tc isgenerallypreferred. 99m Chapter 6: Technical for surgery parathyroid ofprobe-guided adenomas aspects Tc-sestamibi dose 99m Tc-sestamibi - - - 35 99m by means of dual-tracer obtained are images localising day, first the On protocol. different-day a is centre our in would be preferable. The protocol developed nodular goitre so that a different-day protocol even greater in areas with a high prevalence of be to expected be would problem This ing. schedul patient efficient and MIRS) > (BNE respect to the need for operating theatre time with BNE and MIRS between differences the the uncertainty of the scintigraphic results and presents disadvantages some givenpractical and surgery. However, Norman’s protocol also radiotracer dose is required for both imaging single a and day same the on performed are because perspective cost-analysis a from attractive is Norman’sprotocol administration. diotracer ra after h 2–3 within performed is MIRS and technique scintigraphic dual-phase the by tamibi dose protocol and our low our and protocol dose tamibi Norman’shigh both with reported been have results favourable Nevertheless, 99m tive results in parathyroid adenoma with rapid nega fewerfalse (b) and 3) (Table personnel exposure to the patient and operating theatre radiation less (a) advantages: major two has surgery. The low in the operating theatre a few minutes before MBq 37 MIRS, usually within 1 week of imaging, a low of day the On ultrasound. neck with bined Tc-sestamibi subtraction scintigraphy com Tc-sestamibi washout. 99m 99m Tc-sestamibigivendirectly is dose Tc-sestamibi scintigraphy and MIRS 99m Tc-sestamibi dose protocol 99m Tc-pertechnetate/ 99m 99m Tc-ses Tc-ses ------EANM Table 1. Steps in minimally invasive radioguided surgery (MIRS) of parathyroid adenomas using the low 99mTc-sestamibi dose protocol developed in our centre

Blood samples are drawn from a peripheral vein both before commencing surgery and 10 min following the removal of the parathyroid adenoma to measure intra-operative QPTH levels

37 MBq of 99mTc-sestamibi is injected in the operating theatre 10 min before the start of surgery

Prior to surgical incision, the patient’s neck is scanned with an 11-mm collimated probe to localise the site with the highest count rate, corresponding to the cutaneous projection of the parathyroid adenoma

A transverse midline neck access (approximately 1 cm above the sternal notch) is preferred because conversion to BNE is easily obtained if necessary

An 11-mm collimated probe is repeatedly inserted through a 2-cm skin incision, guiding the surgeon to the maximum count rate area corresponding to the parathyroid adenoma

In some patients with a parathyroid adenoma located deep in the neck, ligature of the middle thyroid vein and of the inferior thyroid artery is required

Radioactivity of the parathyroid adenoma, thyroid gland and background is measured with the probe

Radioactivity is measured ex vivo to confirm successful removal of parathyroid tissue

Radioactivity of the empty operation site is checked to evaluate the completeness of para- thyroid tissue removal

Tissue ratios are calculated (P/B, P/T etc.)

QPTH, quick parathyroid hormone; BNE, bilateral neck exploration; P/B, parathyroid to back- ground ratio; P/T, parathyroid to thyroid ratio

36 TN=thyroid nodule B=background T=thyroid P=parathyroid pHPT patients) Table2. prevalence ofnodulargoitre. tocol appears preferable in areas with a higher of nodular goitre whilst our different-day pro be preferable in patients with a low likelihood is likely that Norman’s single-day protocol will major intra-operative surgical complications. It without approximately96–98%, of adenoma parathyroid of detection intra-operative the in rate success a with protocol, dose tamibi • TN/P ratio=0.5–1.5(mean1.0±0.4) bed/Bratio=0.9–1.1(mean1.0±0.03) • Empty-P • T/B ratio=1.5–1.8(mean1.6±0.1) • P/Tratio=1.1–2.8(mean1.5±0.4) • P/Bratio=1.6–4.8(mean2.6±0.5) Probe tissue ratios calculated during MIRS for parathyroid adenoma removal (n=355 removal adenoma parathyroidfor MIRS during calculated ratios Probetissue

Chapter 6: Technical for surgery parathyroid ofprobe-guided adenomas aspects - 37 lower post-surgical timeand(g)lower costs. possibility of hospital same-day discharge, (f) the (e) time, recovery hospital shorter a (d) anaesthesia, local under MIRS performing of (b) a shorter operating time, (c) the possibility skin incision with favourable cosmetic results, small a (a) as: summarised be can BNE tional tradi over MIRS of advantages principal the Irrespective of the type of MIRS protocol used, - EANM Table 3. Radiation dose to operating theatre personnel during MIRS with the low (37 MBq) 99mTc-sestamibi dose protocol used in our centre

µGy/hour µGy/year* Surgeon’s body 1.2 120 Surgeon’s hands 5.0 500 Anaesthesiologist 0.7 70 Instrument nurse 1.1 110 Other nurses 0.1 10

*Estimated for 100 interventions, each lasting 60 min

Figure 1. Preoperative dual-tracer parathyroid subtraction scintigraphy. Left image: 99mTc-pertech- netate scan showing a normal thyroid gland. Middle image: 99mTc-sestamibi scan showing an area of radiotracer uptake juxtaposed to the lower pole of the left thyroid lobe. Right image: Subtraction (99mTc-sestamibi-99mTc-pertechnetate) image, clearly showing a left inferior para- thyroid adenoma. This patient was offered MIRS.

38 sestamibi-avid thyroid nodulesinboththyroid lobes multiple with goitre multinodular and adenoma parathyroid solitary a of coexistence showing a left superior parathyroid adenoma. This patient was excluded from MIRS due to the sestamibi uptake. the to similar picture a lobe). thyroid left the in one lobe, thyroid right the (threein nodules hyperfunctioning some goitrewith multinodular a showing scan netate Figure 2. Preoperative dual-tracer parathyroid subtraction scintigraphy. Right Right image 99m Chapter 6: Technical for surgery parathyroid ofprobe-guided adenomas aspects Tc-pertechnetate image plus a left superior area of exclusive of area superior left a plus image Tc-pertechnetate : subtraction ( 99m 39 Tc-sestamibi- Middle image Middle 99m Tc-pertechnetate) image clearly : 99m Tc-sestamibi scan showing scan Tc-sestamibi Left image : 99m Tc-pertech 99m 99m Tc- Tc- - EANM References

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Berna L, Sitges-Serra A. Parathyroid scintigraphy with scintigraphy Parathyroid A. Sitges-Serra L, Berna Administration of Radioactive Substances Advisory Advisory Substances Radioactive of Administration Ogard CG, Vestergaard H, Thomsen JB, Jakobsen H, Jakobsen JB, Thomsen H, VestergaardCG, Ogard Protection. Radiation on Commission International Cook GJ, Wong JC, Smellie WJ, Young AE, Maisey MN, Fo Hesslewood S. European system for reporting adverse Europeanforsystemreporting S. Hesslewood Broe J, Lee D,WF,Broussard Evans EE, Kim IW, Gayed H. Chen Thallium-per M, DreznerJ, Bianco J,Frydman Sundin A, Johansson C, Hellman P, Bergstrom M, Ahl P,M, Hellman Bergstrom C, Johansson A, Sundin 99mTc-sestamibiD.ParathyroidNguyenwith imaging ------EANM Chapter 3 Chapter 6

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