Purpose. To perform an overview about the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using different radiopharmaceuticals in recurrent medullary thyroid carcinoma (MTC) based on biochemical findings (increased tumor marker levels after primary surgery). Methods. A comprehensive literature search of studies published in PubMed/MEDLINE, Scopus, and Embase databases through February 2012 regarding PET or PET/CT in patients with recurrent MTC was performed. Results. Twenty-nine studies comprising 714 patients with suspected recurrent MTC were retrieved. Twenty-seven articles evaluated the role of fluorine-18-fluorodeoxyglucose (FDG) PET or PET/CT in recurrent MTC with conflicting results. Diagnostic accuracy of FDG-PET and PET/CT increased in MTC patients with higher calcitonin and carcinoembryonic antigen values, suggesting that these imaging methods could be very useful in patients with more advanced and aggressive disease. Eight articles evaluated the role of fluorine-18-dihydroxyphenylalanine (FDOPA) PET or PET/CT in recurrent MTC reporting promising results. Overall, FDOPA seems to be superior but complementary compared to FDG in detecting recurrent MTC. Few studies evaluating other PET tracers are also discussed. Conclusions. PET radiopharmaceuticals reflect different metabolic pathways in MTC. FDOPA seems to be the most useful PET tracer in detecting recurrent MTC based on rising levels of tumor markers. FDG may complement FDOPA in patients with more aggressive MTC. 1. Introduction Medullary thyroid carcinoma (MTC) is a slow-growing neuroendocrine tumor originating from parafollicular C cells. MTC accounts for approximately 5% of thyroid carcinomas, occurring in either sporadic (75% of cases) or familial forms (25% of cases). This tumor is frequently aggressive; most frequent sites of metastatic disease are cervical and mediastinal lymph nodes, lungs, liver, and bone. The main treatment for MTC is surgical resection that is the only strategy for potential cure; in patients with metastatic disease therapeutic options are limited as this tumor does not concentrate radioiodine and shows poor response to chemotherapy and radiation therapy [1]. Also targeted therapy with vandetanib seems to show promising results in the treatment of patients with metastatic/recurrent MTC [1]. Serum calcitonin represents the most sensitive and accurate tumor marker in the postoperative management and surveillance of MTC. In about one third of patients with MTC lesions also carcinoembryonic antigen (CEA) levels may be increased and this
References
[1]
S. C. Pitt and J. F. Moley, “Medullary, anaplastic, and metastatic cancers of the thyroid,” Seminars in Oncology, vol. 37, no. 6, pp. 567–579, 2010.
[2]
American Thyroid Association Guidelines Task Force, R. T. Kloos, C. Eng et al., “Medullary thyroid cancer: management guidelines of the American Thyroid Association,” Thyroid, vol. 19, no. 6, pp. 565–612, 2009.
[3]
V. Rufini, G. Treglia, G. Perotti, L. Leccisotti, M. L. Calcagni, and D. Rubello, “Role of PET in medullary thyroid carcinoma,” Minerva Endocrinologica, vol. 33, no. 2, pp. 67–73, 2008.
[4]
V. Rufini, P. Castaldi, G. Treglia et al., “Nuclear medicine procedures in the diagnosis and therapy of medullary thyroid carcinoma,” Biomedicine and Pharmacotherapy, vol. 62, no. 3, pp. 139–146, 2008.
[5]
G. Treglia, P. Castaldi, M. F. Villani et al., “Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 39, pp. 569–580, 2012.
[6]
S. Kauhanen, C. Schalin-J？ntti, M. Sepp？nen et al., “Complementary roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in medullary thyroid cancer,” Journal of Nuclear Medicine, vol. 52, pp. 1855–1863, 2011.
[7]
E. Ozkan, C. Soydal, O. N. Kucuk, E. Ibis, and G. Erbay, “Impact of 18F-FDG PET/CT for detecting recurrence of medullary thyroid carcinoma,” Nuclear Medicine Communications, vol. 32, pp. 1162–1168, 2011.
[8]
P. Gómez-Camarero, A. Ortiz-de Tena, I. Borrego-Dorado et al., “Evaluation of efficacy and clinical impact of 18F-FDG-PET in the diagnosis of recurrent medullary thyroid cancer with increased calcitonin and negative imaging test,” Revista Espa？ola de Medicina Nuclear. In press.
[9]
I. Pa？yga, A. Kowalska, D. G？sior-Perczak et al., “The role of PET-CT scan with somatostatin analogue labelled with gallium-68 (68Ga-DOTA-TATE PET-CT) in diagnosing patients with disseminated medullary thyroid carcinoma (MTC),” Endokrynologia Polska, vol. 61, no. 5, pp. 507–511, 2010.
[10]
H. W. Jang, J. Y. Choi, J. I. Lee et al., “Localization of medullary thyroid carcinoma after surgery using 11C-methionine pet/ct: comparison with 18F-FDG PET/CT,” Endocrine Journal, vol. 57, no. 12, pp. 1045–1054, 2010.
[11]
M. Luster, W. Karges, K. Zeich et al., “Clinical value of 18-fluorine-fluorodihydroxyphenylalanine positron emission tomography/computed tomography in the follow-up of medullary thyroid carcinoma,” Thyroid, vol. 20, no. 5, pp. 527–533, 2010.
[12]
E. Skoura, P. Rondogianni, M. Alevizaki et al., “Role of [18F]FDG-PET/CT in the detection of occult recurrent medullary thyroid cancer,” Nuclear Medicine Communications, vol. 31, no. 6, pp. 567–575, 2010.
[13]
M. C. Marzola, M. R. Pelizzo, M. Ferdeghini et al., “Dual PET/CT with 18F-DOPA and 18F-FDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: comparison with conventional imaging,” European Journal of Surgical Oncology, vol. 36, no. 4, pp. 414–421, 2010.
[14]
T. V. Bogsrud, D. Karantanis, M. A. Nathan et al., “The prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in patients with suspected residual or recurrent medullary thyroid carcinoma,” Molecular Imaging and Biology, vol. 12, no. 5, pp. 547–553, 2010.
[15]
B. G. Conry, N. D. Papathanasiou, V. Prakash et al., “Comparison of 68Ga-DOTATATE and 18F- fluorodeoxyglucose PET/CT in the detection of recurrent medullary thyroid carcinoma,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 37, no. 1, pp. 49–57, 2010.
[16]
M. Beheshti, S. P？cher, R. Vali et al., “The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PET-CT,” European Radiology, vol. 19, no. 6, pp. 1425–1434, 2009.
[17]
A. Faggiano, F. Grimaldi, L. Pezzullo et al., “Secretive and proliferative tumor profile helps to select the best imaging technique to identify postoperative persistent or relapsing medullary thyroid cancer,” Endocrine-Related Cancer, vol. 16, no. 1, pp. 225–231, 2009.
[18]
K. P. Koopmans, J. W. B. De Groot, J. T. M. Plukker et al., “18F-dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer: relation to tumor differentiation,” Journal of Nuclear Medicine, vol. 49, no. 4, pp. 524–531, 2008.
[19]
D. Rubello, L. Rampin, C. Nanni et al., “The role of 18F-FDG PET/CT in detecting metastatic deposits of recurrent medullary thyroid carcinoma: a prospective study,” European Journal of Surgical Oncology, vol. 34, no. 5, pp. 581–586, 2008.
[20]
A. Oudoux, P. Y. Salaun, C. Bournaud et al., “Sensitivity and prognostic value of positron emission tomography with F-18-fluorodeoxyglucose and sensitivity of immunoscintigraphy in patients with medullary thyroid carcinoma treated with anticarcinoembryonic antigen-targeted radioimmunotherapy,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 12, pp. 4590–4597, 2007.
[21]
A. L. Giraudet, D. Vanel, S. Leboulleux et al., “Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 11, pp. 4185–4190, 2007.
[22]
R. Czepczyński, M. G. Parisella, J. Kosowicz et al., “Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 34, no. 10, pp. 1635–1645, 2007.
[23]
B. Beuthien-Baumann, A. Strumpf, J. Zessin, J. Bredow, and J. Kotzerke, “Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 34, no. 10, pp. 1604–1609, 2007.
[24]
S. C. Ong, H. Sch？der, S. G. Patel et al., “Diagnostic accuracy of 18F-FDG PET in restaging patients with medullary thyroid carcinoma and elevated calcitonin levels,” Journal of Nuclear Medicine, vol. 48, no. 4, pp. 501–507, 2007.
[25]
A. Iagaru, R. Masamed, P. A. Singer, and P. S. Conti, “Detection of occult medullary thyroid cancer recurrence with 2-Deoxy-2-[F-18]fluoro-d-glucose-PET and PET/CT,” Molecular Imaging and Biology, vol. 9, no. 2, pp. 72–77, 2007.
[26]
M. Gotthardt, M. P. Béhé, D. Beuter et al., “Improved tumour detection by gastrin receptor scintigraphy in patients with metastasised medullary thyroid carcinoma,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 33, no. 11, pp. 1273–1279, 2006.
[27]
J. W. B. de Groot, T. P. Links, P. L. Jager, T. Kahraman, and J. T. M. Plukker, “Impact of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in patients with biochemical evidence of recurrent or residual medullary thyroid cancer,” Annals of Surgical Oncology, vol. 11, no. 8, pp. 786–794, 2004.
[28]
S. Szakáll Jr., O. ésik, G. Bajzik et al., “18F-FDG PET detection of lymph node metastases in medullary thyroid carcinoma,” Journal of Nuclear Medicine, vol. 43, no. 1, pp. 66–71, 2002.
[29]
M. Diehl, J. H. Risse, K. Brandt-Mainz et al., “Fluorine-18 fluorodeoxyglucose positron emission tomography in medullary thyroid cancer: results of a multicentre study,” European Journal of Nuclear Medicine, vol. 28, no. 11, pp. 1671–1676, 2001.
[30]
S. Hoegerle, C. Altehoefer, N. Ghanem, I. Brink, E. Moser, and E. Nitzsche, “18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels,” European Journal of Nuclear Medicine, vol. 28, no. 1, pp. 64–71, 2001.
[31]
K. Brandt-Mainz, S. P. Müller, R. G？rges, B. Saller, and A. Bockisch, “The value of fluorine-18 fluorodeoxyglucose PET in patients with medullary thyroid cancer,” European Journal of Nuclear Medicine, vol. 27, no. 5, pp. 490–496, 2000.
[32]
S. Adams, R. Baum, T. Rink, P. M. Schumm-Dr？ger, K. H. Usadel, and G. H？r, “Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours,” European Journal of Nuclear Medicine, vol. 25, no. 1, pp. 79–83, 1998.
[33]
T. J. Musholt, P. B. Musholt, F. Dehdashti, and J. F. Moley, “Evaluation of fluorodeoxyglucose-positron emission tomographic scanning and its association with glucose transporter expression in medullary thyroid carcinoma and pheochromocytoma: a clinical and molecular study,” Surgery, vol. 122, no. 6, pp. 1049–1061, 1997.
[34]
S. Adams, R. P. Baum, A. Hertel, P. M. Schumm-Dr？ger, K. H. Usadel, and G. H？r, “Metabolic (PET) and receptor (SPET) imaging of well- and less well- differentiated tumours: comparison with the expression of the Ki-67 antigen,” Nuclear Medicine Communications, vol. 19, no. 7, pp. 641–647, 1998.
[35]
R. Czepczyński, J. Kosowicz, K. Ziemnicka, R. Miko？ajczak, M. Gryczyńska, and J. Sowiński, “The role of scintigraphy with the use of 99mTc-HYNIC-TOC in the diagnosis of medullary thyroid carcinoma,” Endokrynologia Polska, vol. 57, no. 4, pp. 431–435, 2006.
[36]
M. Gotthardt, A. Battmann, H. H？ffken et al., “18F-FDG PET, somatostatin receptor scintigraphy, and CT in metastatic medullary thyroid carcinoma: a clinical study and an analysis of the literature,” Nuclear Medicine Communications, vol. 25, no. 5, pp. 439–443, 2004.
[37]
A. Boér, S. Szakáll Jr., I. Klein et al., “FDG PET imaging in hereditary thyroid cancer,” European Journal of Surgical Oncology, vol. 29, no. 10, pp. 922–928, 2003.
[38]
S. Szakáll Jr., G. Bajzik, I. Repa et al., “FDG PET scan of metastases in recurrent medullary carcinoma of the thyroid gland,” Orvosi Hetilap, vol. 143, no. 21, pp. 1280–1283, 2002.
[39]
P. S. Conti, J. M. Durski, F. Bacqai, S. T. Grafton, and P. A. Singer, “Imaging of locally recurrent and metastatic thyroid cancer with positron emission tomography,” Thyroid, vol. 9, no. 8, pp. 797–804, 1999.
[40]
G. Treglia, M. F. Villani, A. Giordano, and V. Rufini, “Detection rate of recurrent medullary thyroid carcinoma using fluorine-18 fluorodeoxyglucose positron emission tomography: a meta-analysis,” Endocrine. In press.
[41]
S. Kauhanen, M. Seppa？nen, J. Ovaska et al., “The clinical value of [18F]fluorodihydroxyphenylalanine positron emission tomography in primary diagnosis, staging, and restaging of neuroendocrine tumors,” Endocrine-Related Cancer, vol. 16, no. 1, pp. 255–265, 2009.
[42]
G. Treglia, P. Castaldi, G. Rindi, A. Giordano, and V. Rufini, “Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis,” Endocrine. In press.
