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      PET Imaging in Recurrent Medullary Thyroid Carcinoma

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          Abstract

          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.

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          Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels.

          J P Travagli, Sophie Leboulleux, Linda Chami … (2007)
          Because calcitonin level remains elevated after initial treatment in many medullary thyroid carcinoma (MTC) patients without evidence of disease in the usual imaging work-up, there is a need to define optimal imaging procedures. Fifty-five consecutive elevated calcitonin level MTC patients were enrolled to undergo neck and abdomen ultrasonography (US); neck, chest, and abdomen spiral computed tomography (CT); liver and whole-body magnetic resonance imaging (MRI); bone scintigraphy; and 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/CT scan (PET). Fifty patients underwent neck US, CT, and PET, and neck recurrence was demonstrated in 56, 42, and 32%, respectively. Lung and mediastinum lymph node metastases in the 55 patients were demonstrated in 35 and 31% by CT and in 15 and 20% by PET. Liver imaging with MRI, CT, US, and PET in 41 patients showed liver in 49, 44, 41, and 27% patients, respectively. Bone metastases in 55 patients were demonstrated in 35% by PET, 40% by bone scintigraphy, and 40% by MRI; bone scintigraphy was complementary with MRI for axial lesions but superior for the detection of peripheral lesions. Ten patients had no imaged tumor site despite elevated calcitonin level (median 196 pg/ml; range 39-816). FDG uptake in neoplastic foci was higher in progressive patients but with a considerable overlap with stable ones. The most efficient imaging work-up for depicting MTC tumor sites would consist of a neck US, chest CT, liver MRI, bone scintigraphy, and axial skeleton MRI. FDG PET scan appeared to be less sensitive and of low prognostic value.
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            Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours.

            Kyle Baum, Charles Adams, P-M Schumm-Draeger … (1997)
            Scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide or pentavalent technetium-99m-dimercaptosuccinic acid [99mTc(V)-DMSA] has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased fluorodeoxyglucose (FDG) uptake is associated with malignancy. The aim of this study was to compare the value of fluorine-18 FDG positron emission tomography (PET) with that of somatostatin receptor scintigraphy (SS-R) and dual-radionuclide scintigraphy [SS-R and 99mTc(V)-DMSA = DNS] in detecting malignant neuroendocrine tumours. Fifteen patients with metastasizing gastroenteropancreatic tumours (GEP tumours; n = 7), medullary thyroid carcinomas (MTCs; n = 8) and elevated tumour markers [GEP tumours: 5-hydroxyindoleacetic acid, insulin; MTCs: calcitonin, carcinoembryonic antigen (CEA)] were studied. Prior to PET, all patients with GEP tumours underwent SS-R. DNS was performed in all patients with MTC. Patients had been fasting for at least 12 h and normal glucose plasma levels were confirmed. Sixty minutes after intravenous administration of 18F-FDG (mean: 374 MBq) whole-body PET and regional scans were performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). In two patients with less-differentiated GEP tumours associated with high proliferative activity and increased FDG uptake, SS-R failed to detect any lesion. In comparison, in four patients with well-differentiated GEP tumours showing low proliferative activity, SS-R localized four primary tumours, 22 lymph node metastases and 18 malignant liver lesions, whereas 18F-FDG PET demonstrated normal distribution. In one patient with a metastasizing carcinoid (medium proliferative activity) SS-R localized multiple metastases, whereas PET demonstrated low FDG uptake in all known metastases. In patients with recurrent MTC and rapidly increasing CEA levels DNS detected only three lesions in two patients, whereas PET demonstrated one pulmonary, three osseous, 20 mediastinal, ten locoregional, and four liver metastases in seven patients. Twenty-nine malignant lesions were confirmed by follow-up and nine lymph node metastases could be surgically removed. In conclusion, PET imaging of gastroenteropancreatic tumours revealed increased glucose metabolism only in less-differentiated GEP tumours with high proliferative activity and metastasizing MTC associated with rapidly increasing CEA levels. Therefore, additional 18F-FDG PET should be performed only if SS-R or DNS is negative.
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              Diagnostic accuracy of 18F-FDG PET in restaging patients with medullary thyroid carcinoma and elevated calcitonin levels.

              Sita Patel, Mithat Gonen, John Tuttle … (2007)
              Medullary thyroid carcinoma (MTC) is a rare endocrine tumor arising from the C-cells of the thyroid gland. Calcitonin is the principal serum tumor marker. A rising calcitonin level after total thyroidectomy for localized disease generally indicates residual, recurrent, or metastatic disease. The role of (18)F-FDG PET in MTC remains somewhat unclear. We reviewed our own experience with (18)F-FDG PET in postthyroidectomy MTC patients with elevated calcitonin. From our database, we identified patients with suspected residual, recurrent, or metastatic MTC and elevated calcitonin who had been referred for (18)F-FDG PET between January 2000 and October 2005. (18)F-FDG PET findings were classified as positive or negative on the basis of visual interpretation of the scan. Standardized uptake values (SUVs) were also calculated. The (18)F-FDG PET findings were verified by histopathologic examination, when available, or other imaging studies and clinical follow-up. Any negative (18)F-FDG PET result was considered false-negative. Twenty-eight patients underwent a total of 38 (18)F-FDG PET studies. Calcitonin levels ranged from 106 to 541,000 pg/mL (median, 7,260 pg/mL). There were 23 true-positive, 1 false-positive, and 14 false-negative (18)F-FDG PET scans, yielding an overall sensitivity of 62%. There was no true-positive finding when calcitonin levels were below 509 pg/mL (n = 5). Using an arbitrary cutoff of 1,000 pg/mL, we found that the sensitivity in scans with calcitonin levels greater than 1,000 pg/mL increased to 78% (21/27; 95% confidence interval, 58%-91%). The mean SUV of all lesions with (18)F-FDG uptake was 5.3 +/- 3.2 (range, 2.0-15.9). Among the 14 patients with false-negative (18)F-FDG PET findings, 8 had concurrent anatomic imaging studies and only 2 of these had positive findings. (18)F-FDG PET can detect residual, recurrent, or metastatic MTC with a reasonable sensitivity of 78% when the calcitonin level is above 1,000 pg/mL but appears of limited use if the calcitonin level is below 500 pg/mL.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Imaging
                Journal ID (iso-abbrev): Int J Mol Imaging
                Journal ID (publisher-id): IJMI
                Title: International Journal of Molecular Imaging
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-1712
                ISSN (Electronic): 2090-1720
                Publication date (Print): 2012
                Publication date (Electronic): 18 July 2012
                Volume: 2012
                Electronic Location Identifier: 324686
                Affiliations
                1Institute of Nuclear Medicine, Catholic University of the Sacred Heart, 00168 Rome, Italy
                2Department of Nuclear Medicine and PET-CT Centre, Oncology Institute of Southern Switzerland, Street Ospedale 12, 6500 Bellinzona, Switzerland
                Author notes

                Academic Editor: Francesco S. Celi

                Article
                DOI: 10.1155/2012/324686
                PMC ID: 3407631
                PubMed ID: 22852077
                SO-VID: 3ef9eb9d-51bb-4ca1-841d-3aacd51aabba
                Copyright © Copyright © 2012 Giorgio Treglia et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 April 2012
                Date accepted : 21 May 2012
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Molecular biology
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                ScienceOpen disciplines: Molecular biology

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