Review Nuclear medicine procedures in the diagnosis and therapy of medullary thyroid carcinoma Vittoria Rufini a , Paola Castaldi a , Giorgio Treglia a , Germano Perotti a , Milton D. Gross b , Adil Al-Nahhas c , Domenico Rubello d, * a Institute of Nuclear Medicine, Universita ` Cattolica del Sacro Cuore, Rome, Italy b Department of Nuclear Medicine, Veneran Affairs Health System, Ann Arbor, MI, USA c Department of Nuclear Medicine, Hammersmith Hospital, London, UK d Nuclear Medicine, PET Unit, ‘‘S. Maria della Misericordia’’ Hospital, Istituto Oncologico Veneto (IOV)-IRCCS, Viale Tre Martiri, 140, 45100 Rovigo, Italy Received 9 July 2007; accepted 25 July 2007 Available online 20 August 2007 Abstract Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating in the parafollicular cells (C cells) of the thyroid and secretes both calcitonin and carcino-embryonic antigen (CEA). Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary thyroid nodule; the diagnosis can be made preoperatively by fine-needle aspiration or by calcitonin assay, though it is usually established at the time of surgery. In the diagnostic assessment of MTC, nuclear medicine imaging provides its con- tribution mainly in the post-operative work-up to detect residual/recurrent tumor. For such purpose a number of radiopharmaceuticals, which take advantage of the specific expression of receptors (the somatostatin analogue 111 In-octreotide), hormone transporters (radiolabelled MIBG) or molecular targets (radiolabelled anti-CEA monoclonal antibodies) by MTC lesions are available; these tracers may be used also for the palliative treatment of advanced MTC. Interesting perspectives for MTC imaging are offered by PET radiopharmaceuticals. Ó 2007 Elsevier Masson SAS. All rights reserved. Keywords: Medullary thyroid carcinoma; Radiopharmaceuticals; Diagnosis; Therapy 1. Background Medullary thyroid carcinoma (MTC) is a rare neuroendo- crine tumor originating in the parafollicular cells (C cells), which are of neural crest origin and secrete calcitonin as well as a wide variety of other substances, including car- cino-embryonic antigen (CEA), somatostatin and vasoactive intestinal polipeptide (VIP) [1]. Since its first description almost 50 years ago, important knowledge has been acquired regarding pathogenesis and clin- ical management of MTC [2]. The reported prevalence is 3e 12% of all thyroid cancers. MTC may occur in either sporadic or familial forms; the latter (w25% of cases) include isolated MTC in which thyroid cancer is the only manifestation of the disease, and multiple endocrine neoplasia type 2 (MEN 2A and MEN 2B) (Table 1). Familial MTC, which has an autoso- mal dominant pattern of transmission, is caused by a germline mutation in the RET proto-oncogene and its initial sign is dif- fuse C cell hyperplasia followed by multiple microscopic foci of carcinoma and then macroscopic MTC [3]. At present, ge- netic testing is an integral part in the clinical management of MTC and should be performed in all patients presenting with clinically evident tumor, since a germline RET mutation can be found in approximately 6e10% of patients with MTC who have no family history (index cases) [4,5]. Clinically, patients with sporadic MTC as well as the index cases of familial MTC usually present with a palpable thyroid * Corresponding author. Tel.: þ39 0 39 425 4427; fax: þ39 0 39 425 4434. E-mail address: domenico.rubello@libero.it (D. Rubello). 0753-3322/$ - see front matter Ó 2007 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.biopha.2007.07.011 Available online at www.sciencedirect.com Biomedicine & Pharmacotherapy 62 (2008) 139e146 www.elsevier.com/locate/biopha