Increased Gallium-68 DOTATOC Uptake in Normal Thyroid Glands

Abstract

Increased Ga-68 DOTATOC uptake for normal and goitrous and/or nodular thyroids has previously been reported for a small number of patients. The aim of this study was to reevaluate these preliminary findings with larger patient numbers and to determine possible variables, which might influence the quantification of Ga-68 DOTATOC uptake in normal and pathologic thyroid tissues. Ga-68 DOTATOC PET scans of 165 patients classified for various thyroid pathologies were analyzed by the so-called region of interest technique for Ga-68 DOTATOC uptake and the patient's history, thyroid ultrasound, TSH, and anti-TPO antibodies. Thyroid glands without any pathology showed a clearly detectable uptake of Ga-68 DOTATOC with a large variability and significantly higher target to background ratios for men as compared to women. In 8 cases of normal thyroids with an increased uptake, follow-up examinations after 6–14 months did not show any thyroid pathology. An increased DOTATOC uptake (target to background ratio >3.4) was found in hot nodules, disseminated thyroid autonomy, and in most cases (5 of 8) of active Hashimoto's disease. In Ga-68 DOTATOC PET, normal thyroid glands show a clearly detectable radiotracer uptake with a large variability and significantly higher target to background ratios in male patients. All patients with thyroid autonomy and most patients with active Hashimoto's disease have an increased thyroid DOTATOC uptake.

Key words

Ga-68 DOTATOC - PET - thyroid gland - SSTR - relative quantification - normal thyroid - thyroid nodules

References

• 1 Danila DC, Haidar JN, Zhang X, Katznelson L, Culler MD, Klibanski A. Somatostatin receptor-specific analogs: effects on cell proliferation and growth hormone secretion in human somatotroph tumors.  J Clin Endocrinol Metab. 2001;  86 2976-2981
• 2 Krantic S, Goddard I, Saveanu A, Giannetti N, Fombonne J, Cardoso A, Jaquet P, Enjalbert A. Novel modalities of somatostatin actions.  Eur J Endocrinol. 2004;  151 643-655
• 3 Becker W, Schrell U, Buchfelder M, Hensen J, Wendler J, Gramatzki M, Wolf F. Somatostatin receptor expression in the thyroid demonstrated with 111In-octreotide scintigraphy.  Nuklearmedizin. 1995;  34 100-103
• 4 Rambaldi PF, Cuccurullo V, Briganti V, Mansi L. The present and future role of 111In Pentetreotide in the PET era.  Q J Nucl Med Mol Imaging. 2005;  49 225-235
• 5 Hofland LJ, Lamberts SW, van Hagen PM, Reubi JC, Schaeffer J, Waaijers M, van Koetsveld PM, Srinivasan A, Krenning EP, Breeman WA. Crucial role for somatostatin receptor subtype 2 in determining the uptake of 111In-DTPA-DPhe1 octreotide in somatostatin receptor-positive organs.  J Nucl Med. 2003;  44 1315-1321
• 6 Maecke HR, Hofmann M, Haberkorn U. (68)Ga-labeled peptides in tumor imaging.  J Nucl Med. 2005;  46 172S-178S
• 7 Koukouraki S, Strauss LG, Georgoulias V, Eisenhut M, Haberkorn U, Dimitrakopoulou-Strauss A. Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.  Eur J Nucl Med Mol Imaging. 2006;  33 1115-1122
• 8 Patel YC, Srikant CB. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1–5).  Endocrinology. 1994;  135 2814-2817
• 9 Bruns C, Raulf F, Hoyer D, Schloos J, Lübbert H, Weckbecker G. Binding properties of somatostatin receptor subtypes.  Metabolism. 1996;  45 17-20
• 10 Ain KB, Taylor KD. Somatostatin analogs affect proliferation of human thyroid carcinoma cell lines in vitro.  J Clin Endocrinol Metab. 1994;  78 1097-1102
• 11 Medina DL, Toro M-J, Santisteban P. Somatostatin interferes with thyrotropin-induced G1-S transition mediated by cAMP-dependent protein kinase and phosphatidylinositol 3-kinase. Involvement of RhoA and cyclin E x cyclin-dependent kinase 2 complexes.  J Biol Chem. 2000;  275 15549-15556
• 12 Lattuada D, Casnici C, Crotta K, Mastrotto C, Franco P, Schmid HA, Marelli O. Inhibitory effect of pasireotide and octreotide on lymphocyte activation.  J Neuroimmunol. 2007;  182 153-159
• 13 Medina DL, Velasco JA, Santisteban P. Somatostatin is expressed in FRTL-5 thyroid cells and prevents thyrotropin-mediated down-regulation of the cyclin-dependent kinase inhibitor p27kip1.  Endocrinology. 1999;  140 87-95
• 14 Lincke T, Singer J, Kluge R, Sabri O, Paschke R. Relative quantification of In-111 Pentetreotide and Ga-68 DOTATOC uptake in the thyroid gland and association with thyroid pathologies.  Thyroid. 2009;  19 381-389
• 15 Yüksel M, Eziddin S, Wardelmann E, Biersack HJ. 111In-Pentetreotide uptake in a follicular adenoma of the thyroid gland: a pitfall for 111In-Pentetreotide scintigraphy.  Rev Esp Med Nucl. 2006;  25 316-319
• 16 Koriyama N, Nakazaki M, Hashiguchi H, Aso K, Ikeda Y, Kimura T, Eto H, Hirano H, Nakano S, Tei C. Thyrotropin-producing pituitary adenoma associated with Graves’ disease.  Eur J Endocrinol. 2004;  151 587-594
• 17 Krassas GE, Kahaly GJ. The role of octreoscan in thyroid eye disease.  Eur J Endocrinol. 1999;  140 373-375
• 18 Zatelli MC, degli Uberti EC. Somatostatin receptors: from basic science to clinical approach – thyroid.  Dig Liver Dis. 2004;  36 86-92
• 19 Krummenauer F. Statistics in medical publications: Check lists for Authors.  Klin Monbl Augenheilkd. 2003;  220 362-365
• 20 Druckenthaner M, Schwarzer C, Ensinger C, Gabriel M, Prommegger R, Riccabona G, Decristoforo C. Evidence for Somatostatin receptor 2 in thyroid tissue.  Regul Pept. 2007;  138 32-39
• 21 Kahaly G, Gorges R, Diaz M, Hommel G, Bockisch A. Indium-111-pentetreotide in Graves’ disease.  J Nucl Med. 1998;  39 533-536
• 22 Gorancini S, La Rosa S, De Palma D, Uccella S, Golonia F. Uptake of In-111-pentetreotide by normally functioning nodular goiters.  Clin Nucl Med. 1997;  22 625-627

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