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Diagnostic Nuclear Medicine Investigations in the Management of Thyroid Cancer Susan E.M

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Diagnostic Nuclear Medicine Investigations in the Management of Thyroid Cancer Susan E.M 27 Diagnostic Nuclear Medicine Investigations in the Management of Thyroid Cancer Susan E.M. Clarke Introduction cancer, computed tomography (CT) will detect macroscopic lung metastases, brain and liver metastases, and magnetic resonance imaging Whilst radionuclide imaging of the thyroid has (MRI) has proven sensitivity for detecting long been used in the management of patients marrow involvement. with thyroid cancer, its proven role is the subject Although 131I iodine has been used for over 50 of discussion. 131I iodine has a clearly estab- years to image and treat thyroid cancer, it is in lished place in the imaging and treatment of his- the last 20 years that there has been the devel- tologically proven differentiated papillary and opment of many new radiopharmaceuticals follicular thyroid cancer but the role of radio- that are now being used to image patients with nuclide imaging in diagnosis remains con- thyroid cancer. Whilst many of these remain of troversial. Similarly, in patients with medullary research interest only, 18fluorodeoxyglucose thyroid cancer, radionuclide imaging is utilized (18FDG) is rapidly becoming established as a very variably. It is in the centers where there is valuable agent in patients with 131I iodine scan a close collaboration between the thyroid onco- negative disease. logy service and the nuclear medicine depart- Whilst radionuclide imaging is a comple- ment that the contribution of radionuclide mentary imaging technique to other anatomical imaging is most frequently recognized. imaging methods, it has two main advantages. Diagnostic nuclear medicine techniques may The first is the provision of whole-body infor- be used in the detection of metastatic spread mation that facilitates accurate staging at to the skeleton. The 99mTc diphosphonate bone the time of diagnosis and restaging following scan remains a sensitive method for screening treatment. The second is the potential for for bone metastases and investigating bone therapy with the exchange of a gamma-emitting pain. 99mTc pertechnetate salivary gland imag- radionuclide for a beta or Auger electron ing will identify patients with unilateral or emitter. Uptake of a diagnostic radiopharma- bilateral salivary gland dysfunction including ceutical will identify those patients who may obstruction. benefit from therapy. This is particularly rele- Radionuclide imaging must be considered in vant in patients with recurrent inoperable conjunction with other imaging modalities. In medullary thyroid cancer in whom treatment particular, ultrasound has been demonstrated options are extremely limited with no to be sensitive in detecting cervical lymph significant responses reported to external beam nodes and liver metastases in medullary thyroid radiotherapy or chemotherapy. 341 342 Practical Management of Thyroid Cancer Radionuclide Imaging some countries, such as the UK, nuclear medi- cine imaging may only be undertaken with Facilities appropriate certification of facilities and staff. Nuclear medicine diagnostic investigations for the investigation of thyroid cancer require Radiopharmaceuticals appropriate equipment, trained authorized 99mTc Pertechnetate staff, and a supply of appropriate radiopharma- ceuticals. 99mTc pertechnetate is the most commonly A gamma camera with tomographic capabil- used radiopharmaceutical for routine thyroid ities is essential if high quality studies with imaging with a 6.4h half-life. It combines the appropriate sensitivity are to be achieved. advantages of good imaging characteristics (140 Studies for small volume recurrent disease will keV), availability, and low cost. Unlike the iso- be nondiagnostic if only planar views are topes of iodine, however, it is trapped but not obtained. High resolution, low, medium and organified by thyroid follicular cells and its bio- high energy collimators will be required if the logical half-life within the thyroid is therefore full range of radionuclide investigations is to significantly shorter than the isotope of iodine be performed. Although gamma cameras with that is used for imaging, 123I (Table 27.1). positron emission tomography (PET) capabili- Imaging is performed 20 minutes after intra- ties are currently used for 18FDG-PET imaging, venous injection. 99mTc pertechnetate is also the dedicated PET systems yield better results taken up by the salivary glands and dynamic with small volume disease. studies of salivary gland function before and Nuclear medicine studies require a team of after stimulation with a sialogogue will identify staff. This should include trained technologists, glands that have been damaged by the radiation medical physicists to ensure that equipment is dose from therapeutic administration of 131I functioning optimally and address radiation sodium iodide and those that are functioning protection issues for patients, staff and the but obstructed. public, appropriately trained doctors and radiopharmacists. 123I Sodium Iodide Many radiopharmaceuticals may be pur- chased directly from the manufacturer but 123I sodium iodide is an alternative agent for some, such as 99mTc(V)-dimercaptosuccinic acid imaging the thyroid. Like 99mTc pertechnetate it (DMSA), must be manufactured in-house, has good imaging characteristics with a gamma requiring an approved radiopharmacy facility energy of 159KeV and a half-life of 13.5h. It is and experienced radiopharmacist. both trapped and organified by the thyroid The legislation covering departments of follicular cells and has a marginally higher sen- nuclear medicine varies across the world but in sitivity for detecting nonfunctioning nodules Table 27.1 Radiopharmaceuticals used in thyroid disease Radiopharmaceutical Abbreviation Clinical use 99mTc pertechnetate 99mTc Thyroid nodules, goiter, thyrotoxicosis, ectopic thyroid 123I iodide 123I Thyroid nodules, goiter, ectopic thyroid thyrotoxicosis, dyshormonogenesis 131I iodide 131I Carcinoma of the thyroid, diagnosis and treatment 99mTc isonitrile 99mTc-MIBI Thyroid nodules, Ca thyroid MTC 201Thallous chloride 201Tl Thyroid nodules, Ca thyroid, MTC 18Fluorodeoxyglucose 18FDG Ca Thyroid, MTC, Hürthle cell Ca 99mTc (V) dimercaptosuccinic acid 99mTc(V)-DMSA MTC 123I metaiodobenzylguanidine 123/131I-MIBG MTC diagnosis and treatment 111In octreotide 111In Oct MTC, lymphoma, Hürthle cell Ca 67Gallium gitrate 67Ga Lymphoma Diagnostic Nuclear Medicine Investigations in the Management of Thyroid Cancer 343 than 99mTc pertechnetate. It is, however, signifi- Table 27.2 Biodistribution of 131I 99m cantly more expensive than Tc pertechnetate Normal sites of 131I and is not routinely available. In combination accumulation Nontumor sites of 131I uptake with perchlorate it can be used to assess the Salivary glands Hepatic cysts organification capabilities of nodules. Saliva in mouth Psoriasis Stomach 124I Sodium Iodide Intestine Bladder 124I sodium iodide is a positron-emitting isotope of iodine and has been used in a limited number of dosimetric studies. With its ultrashort half- life and limited availability, its main use is in nized as a tumor-imaging agent since 1976, dosimetry research as it provides excellent data when Cox et al. [2] first demonstrated 201Tl on functional volumes [1]. uptake in a bronchial carcinoma included inad- vertently in the field of view during a myocar- 201 131I Sodium Iodide dial stress study. Since then, Tl uptake has been described in thyroid and breast carcino- 131I iodine in the form of 131I sodium iodide has mas, lymphomas, osteosarcomas, Ewing’s sarco- been used for over 40 years to diagnose and mas, and esophageal cancers [3]. It has poor treat thyrotoxicosis and differentiated thyroid imaging characteristics, however, and non- carcinoma. It is produced by the fission of specific uptake in the myocardium, liver, and uranium-236 and by the neutron bombardment muscles limits its usefulness outside the neck. of stable tellurium in a nuclear reactor. It decays by emissions of gamma radiations 364keV 99mTc Sestamibi (MIBI) (81%), 337keV (7.3%), and 284keV (6%) with 99m beta radiation of Emax 0.606MeV to stable Tc sestamibi (MIBI) uptake is proportional to xenon-131. 131I iodine has a half-life of 8.04 days. blood flow and mitochondrial concentration. Imaging is performed using a high energy col- Although originally developed as a myocardial limator on the gamma camera. Imaging is per- perfusion imaging agent, its role in tumor formed 24–130 hours after oral administration imaging is well proven, with uptake in parathy- of the radiopharmaceutical, either in liquid roid adenomas, breast tumors, and thyroid form or as a capsule. malignancies. The main advantage of 131I sodium iodide as a diagnostic and therapeutic radiopharmaceuti- 99mTc(V) Dimercaptosuccinic Acid cal is its low cost and availability while its main disadvantage is the high energy gamma emis- 99mTc(V) dimercaptosuccinic acid (DMSA) was sions, which has radiation protection implica- initially developed in Japan as a general tumor- tions for staff, relatives, and other patients. The imaging agent [4]. It rapidly became apparent normal biodistribution includes the salivary that its main clinical use is in patients with glands, stomach, and bladder. The bowel is also medullary thyroid cancer (MTC). Sensitivities visualized on delayed studies (Table 27.2). An ranging from 50% [5] to 80% [6,7] have been awareness of the normal biodistribution is reported in patients with primary and recurrent essential for the accurate interpretation of MTC. Images should be acquired 2–3h after whole-body images. Contamination
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