Radionuclide Imaging

Thyroid Factor

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Facilities

Nuclear medicine diagnostic investigations for the investigation of thyroid cancer require appropriate equipment, trained authorized staff, and a supply of appropriate radiopharma-ceuticals.

A gamma camera with tomographic capabilities is essential if high quality studies with appropriate sensitivity are to be achieved. Studies for small volume recurrent disease will be nondiagnostic if only planar views are obtained. High resolution, low, medium and high energy collimators will be required if the full range of radionuclide investigations is to be performed. Although gamma cameras with positron emission tomography (PET) capabilities are currently used for 18FDG-PET imaging, the dedicated PET systems yield better results with small volume disease.

Nuclear medicine studies require a team of staff. This should include trained technologists, medical physicists to ensure that equipment is functioning optimally and address radiation protection issues for patients, staff and the public, appropriately trained doctors and radiopharmacists.

Many radiopharmaceuticals may be purchased directly from the manufacturer but some, such as 99mTc(V)-dimercaptosuccinic acid (DMSA), must be manufactured in-house, requiring an approved radiopharmacy facility and experienced radiopharmacist.

The legislation covering departments of nuclear medicine varies across the world but in some countries, such as the UK, nuclear medicine imaging may only be undertaken with appropriate certification of facilities and staff.

Radiopharmaceuticals

99mTc Pertechnetate

99mTc pertechnetate is the most commonly used radiopharmaceutical for routine thyroid imaging with a 6.4 h half-life. It combines the advantages of good imaging characteristics (140 keV), availability, and low cost. Unlike the isotopes of iodine, however, it is trapped but not organified by thyroid follicular cells and its biological half-life within the thyroid is therefore significantly shorter than the isotope of iodine that is used for imaging, 123I (Table 27.1). Imaging is performed 20 minutes after intravenous injection. 99mTc pertechnetate is also taken up by the salivary glands and dynamic studies of salivary gland function before and after stimulation with a sialogogue will identify glands that have been damaged by the radiation dose from therapeutic administration of 131I sodium iodide and those that are functioning but obstructed.

123I Sodium Iodide

123I sodium iodide is an alternative agent for imaging the thyroid. Like 99mTc pertechnetate it has good imaging characteristics with a gamma energy of 159KeV and a half-life of 13.5h. It is both trapped and organified by the thyroid follicular cells and has a marginally higher sensitivity 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

1311

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, Hurthle 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, Hurthle cell Ca

67Gallium gitrate

67Ga

Lymphoma

than 99mTc pertechnetate. It is, however, significantly more expensive than 99mTc pertechnetate and is not routinely available. In combination with perchlorate it can be used to assess the organification capabilities of nodules.

124I Sodium Iodide

124I sodium iodide is a positron-emitting isotope of iodine and has been used in a limited number of dosimetric studies. With its ultrashort halflife and limited availability, its main use is in dosimetry research as it provides excellent data on functional volumes [1].

131I Sodium Iodide

131I iodine in the form of 131I sodium iodide has been used for over 40 years to diagnose and treat thyrotoxicosis and differentiated thyroid carcinoma. It is produced by the fission of uranium-236 and by the neutron bombardment of stable tellurium in a nuclear reactor. It decays by emissions of gamma radiations 364 keV (81%), 337keV (7.3%), and 284keV (6%) with beta radiation of Emax 0.606 MeV to stable xenon-131.131I iodine has a half-life of 8.04 days. Imaging is performed using a high energy col-limator on the gamma camera. Imaging is performed 24-130 hours after oral administration of the radiopharmaceutical, either in liquid form or as a capsule.

The main advantage of 131I sodium iodide as a diagnostic and therapeutic radiopharmaceuti-cal is its low cost and availability while its main disadvantage is the high energy gamma emissions, which has radiation protection implications for staff, relatives, and other patients. The normal biodistribution includes the salivary glands, stomach, and bladder. The bowel is also visualized on delayed studies (Table 27.2). An awareness of the normal biodistribution is essential for the accurate interpretation of whole-body images. Contamination of the skin and hair with saliva or urine may cause false-positive scans and care must be taken in image interpretation.

201Tl Thallium

201Tl thallium is a potassium analogue and crosses the cell membrane via the sodium-potassium ATPase pump. 201Tl has been recog-

Table 27.2 Biodistribution of 131I

Normal sites of 131I accumulation

Nontumor sites of 131I uptake

Salivary glands

Hepatic cysts

Saliva in mouth

Psoriasis

Stomach

Intestine

Bladder

nized as a tumor-imaging agent since 1976, when Cox et al. [2] first demonstrated 201Tl uptake in a bronchial carcinoma included inadvertently in the field of view during a myocardial stress study. Since then, 201Tl uptake has been described in thyroid and breast carcinomas, lymphomas, osteosarcomas, Ewing's sarcomas, and esophageal cancers [3]. It has poor imaging characteristics, however, and nonspecific uptake in the myocardium, liver, and muscles limits its usefulness outside the neck.

99mTc Sestamibi (MIBI)

99mTc sestamibi (MIBI) uptake is proportional to blood flow and mitochondrial concentration. Although originally developed as a myocardial perfusion imaging agent, its role in tumor imaging is well proven, with uptake in parathyroid adenomas, breast tumors, and thyroid malignancies.

99mTc(V) Dimercaptosuccinic Acid

99mTc(V) dimercaptosuccinic acid (DMSA) was initially developed in Japan as a general tumorimaging agent [4]. It rapidly became apparent that its main clinical use is in patients with medullary thyroid cancer (MTC). Sensitivities ranging from 50% [5] to 80% [6,7] have been reported in patients with primary and recurrent MTC. Images should be acquired 2-3 h after injection and uptake may be observed in both soft-tissue and bone metastases. The isomeric mix of 99mTc(V)-DMSA varies when it is prepared using different commercial kits [8,9]. It is suspected that the poor sensitivity results reported by some workers may be a result of the isomeric composition of their manufactured product. A further explanation for some of the poor results reported may be the patient selection. There is a well-recognized subset of patients in whom the calcitonin level is elevated but stable and in whom no focal disease can be demonstrated for several years. Imaging with 99mTc(V)-DMSA in this subset will yield a significantly lower sensitivity for tumor detection.

Single photon emission computed tomography (SPECT) imaging will increase the sensitivity of lesion detection and will also define the extent of the primary tumor more accurately [10].

The normal biodistribution of 99mTc(V)-DMSA is seen at 2h to be in the nasal mucosa and faintly in the skeleton. Breast uptake may be noted in women. Blood pool activity persists at 2 h and the blood pool of the heart, liver, and spleen may be identified on whole-body imaging. There is no nonspecific tracer uptake observed in the liver, making 99mTc(V)-DMSA one of the few tumor-imaging agents that is able to reliably detect liver metastases. Pituitary uptake may be seen in some patients.

Uptake in sites of MTC ranges from intense to faint, with uptake ratios of greater than 30: 1 observed in some patients with neck recurrence. Uptake in soft-tissue sites appears more intense than is observed in sites of bone metastases. Image quality is generally good, although the lack of nonspecific uptake may make localization of an identified lesion difficult. Studies using the principle of image registration have permitted the merger of image data from the 99mTc(V)-DMSA image with the data from an anatomically precise MRI image. This merged image gives clinically useful information to the surgeon prior to surgery. Image registration also raises the sensitivity of both imaging modalities by increasing the confidence with which small lesions may be diagnosed [9].

111I Indium Octreotide

Like many neuroendocrine tumors, MTC tumors express somatostatin receptors [11]. Somatostatin is a neuropeptide that was discovered in 1978 [12] and has been found to have an inhibitory effect on growth hormone receptors. In animals this peptide appears to inhibit the growth of various malignant tumors [13].

123I/131I Iodine Metaiodobenzylguanidine

Following successful imaging of the adrenal medulla by Wieland et al. [14] in 1980, many groups have studied the uptake of the guane-thidine analogue metaiodobenzylguanidine (MIBG) in neuroectodermally derived tumors including MTC. MIBG is commercially available in many countries labeled with either 123I iodine or 131I iodine. Tomographic imaging as well as planar imaging should be performed to optimize sensitivity. Although not routinely used for diagnostic purposes, a positive scan will indicate a possible therapeutic option. A number of commonly prescribed drugs interfere with the uptake of MIBG and should be avoided or discontinued in patients being considered for diagnostic or therapeutic uses of MIBG (Table 27.3).

18FDG-PET

Radiolabeled fluorodeoxyglucose [18FDG] is the most widely used tracer in PET tumor imaging. A structural analogue of 2-deoxyglucose, FDG is transported into and trapped by tumor cells. 18F is a positron emitter with a 20-minute half-life. The emitted positrons interact with matter with release of two 511KeV gamma photons and it is these that are imaged. A dedicated PET camera and appropriate staff are required for imaging and the short half-life of the tracer together with the high cost of equipment limits availability in many areas of the world. 18FDG accumulation is a marker of metabolic activity and therefore reflects proliferative activity and the number of viable tumor cells.

Monoclonal Antibodies

Several monoclonal antibodies have been used to image patients with MTC. These include 123I-,131I-,and mIn-CEA [15,16],both whole anti-

Table 27.3 Drugs that interfere with MIBG uptake

Tricyclic antidepressants

Labetalol

Reserpine

Sympathomimetics

Antipsychotics

Calcium channel blockers

Cocaine body and fragments, and mIn-anticalcitonin antibody. These various monoclonal antibodies are currently only available on a research basis.

Technetium Study

Cholecystokinin (CCK)-B/Gastrin Receptor Imaging

Amiri-Mosavi et al. in 1999 demonstrated that MTC expressed cholecystokinin-B/gastrin receptors [17]. Behr et al. have demonstrated that CCK-B/gastrin receptors can be detected in the biopsy specimens of patients with MTC but are not found in normal thyroid tissue [18]. This agent is only available on a research basis.

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