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18-03-2024 | Positron Emission Tomography | Mini Review

Somatostatin receptor imaging of thyroid tissue and differentiated thyroid cancer using gallium-68-labeled radiotracers—a review of clinical studies

Authors: Reza Pishdad, Giorgio Treglia, Ami Mehta, Prasanna Santhanam

Published in: Endocrine

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Abstract

Introduction

The rise in thyroid cancer incidence, especially papillary thyroid cancer (PTC), has underscored the need for improved diagnostic methods and management strategies. Herein, we aim to comprehensively review the evolving landscape in thyroid cancer diagnosis and the potential utility of Gallium-68 (Ga-68) based somatostatin receptor imaging.

Methods

We reviewed the clinical studies involving Ga-68 based radiotracers by looking at the following literature databases -PUBMED, EMBASE, WEB OF SCIENCE and COCHRANE. We employed a detailed search strategy with the following search terms; PubMed: (“gallium Ga 68 dotatate” [Supplementary Concept]) AND (“Thyroid Gland”[Mesh] OR “Thyroid Nodule”[Mesh] OR “Thyroid Neoplasms”[Mesh]), Embase (“gallium 68” AND “Thyroid Disease”), Web of Science: (“Gallium 68 and Thyroid”).

Results

A comparison between Ga-68 DOTATATE and Ga-68 DOTANOC showed similar sensitivities but a higher uptake for Ga-68 DOTATATE. Studies comparing Ga-68-based SSTR PET with FDG PET highlighted the potential advantages of both approaches, with Ga-68-based SSTR PET being more specific in certain cases.

Discussion

Ga-68-based somatostatin receptor imaging displays clinical utility in RAI-R DTC, offering valuable insight into detecting skeletal lymph node metastases. Notably, it shows potential as a primary imaging tool, potentially augmenting the role of FDG PET. However, SSTR PET imaging’s efficacy in distinguishing benign from malignant thyroid nodules varies, with a complex interplay of factors influencing its specificity, indicating its value as an adjunct to existing methods, warranting further research for a refined role in thyroid cancer management.

Conclusion

Although study variations exist, Ga-based somatostatin receptor imaging holds potential as a complementary tool alongside diagnostic methods in thyroid cancer diagnosis, with particular relevance to RAI-R DTC. In carefully selected patients demonstrating the presence of Ga-68 DOTATATE avid lesions, further exploration, and investigation into the potential utilization of Lu177 DOTATATE are warranted.
Literature
1.
go back to reference H. Lim, S.S. Devesa, J.A. Sosa, D. Check, C.M. Kitahara, Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA 317(13), 1338–1348 (2017)CrossRefPubMedPubMedCentral H. Lim, S.S. Devesa, J.A. Sosa, D. Check, C.M. Kitahara, Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA 317(13), 1338–1348 (2017)CrossRefPubMedPubMedCentral
2.
go back to reference A. Miranda-Filho, J. Lortet-Tieulent, F. Bray, B. Cao, S. Franceschi, S. Vaccarella et al. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol. 9(4), 225–234 (2021)CrossRefPubMed A. Miranda-Filho, J. Lortet-Tieulent, F. Bray, B. Cao, S. Franceschi, S. Vaccarella et al. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol. 9(4), 225–234 (2021)CrossRefPubMed
3.
go back to reference C.D. Seib, J.A. Sosa, Evolving understanding of the epidemiology of thyroid cancer. Endocrinol. Metab. Clin. North Am. 48(1), 23–35 (2019)CrossRefPubMed C.D. Seib, J.A. Sosa, Evolving understanding of the epidemiology of thyroid cancer. Endocrinol. Metab. Clin. North Am. 48(1), 23–35 (2019)CrossRefPubMed
4.
go back to reference M. Aashiq, D.A. Silverman, S. Na’ara, H. Takahashi, M. Amit, Radioiodine-refractory thyroid cancer: molecular basis of redifferentiation therapies, management, and novel therapies. Cancers (Basel) 11(9), 1382 (2019)CrossRefPubMed M. Aashiq, D.A. Silverman, S. Na’ara, H. Takahashi, M. Amit, Radioiodine-refractory thyroid cancer: molecular basis of redifferentiation therapies, management, and novel therapies. Cancers (Basel) 11(9), 1382 (2019)CrossRefPubMed
5.
6.
go back to reference L. Lorusso, E. Minaldi, G. Esposito, P. Piaggi, V. Bottici, S. Brogioni et al. Radio-iodine refractory thyroid cancer patients: a tailored follow-up based on clinicopathological features. J. Endocrinol. Invest 46(10), 2165–2173 (2023)CrossRefPubMedPubMedCentral L. Lorusso, E. Minaldi, G. Esposito, P. Piaggi, V. Bottici, S. Brogioni et al. Radio-iodine refractory thyroid cancer patients: a tailored follow-up based on clinicopathological features. J. Endocrinol. Invest 46(10), 2165–2173 (2023)CrossRefPubMedPubMedCentral
7.
go back to reference B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26(1), 1–133 (2016)CrossRefPubMedPubMedCentral B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26(1), 1–133 (2016)CrossRefPubMedPubMedCentral
8.
go back to reference J.J. Teunissen, D.J. Kwekkeboom, P.P. Kooij, W.H. Bakker, E.P. Krenning, Peptide receptor radionuclide therapy for non-radioiodine-avid differentiated thyroid carcinoma. J. Nucl. Med. 46(Suppl 1), 107S–114SS (2005)PubMed J.J. Teunissen, D.J. Kwekkeboom, P.P. Kooij, W.H. Bakker, E.P. Krenning, Peptide receptor radionuclide therapy for non-radioiodine-avid differentiated thyroid carcinoma. J. Nucl. Med. 46(Suppl 1), 107S–114SS (2005)PubMed
9.
go back to reference A. Klagge, K. Krause, K. Schierle, F. Steinert, H. Dralle, D. Fuhrer, Somatostatin receptor subtype expression in human thyroid tumours. Horm. Metab. Res 42(4), 237–240 (2010)CrossRefPubMed A. Klagge, K. Krause, K. Schierle, F. Steinert, H. Dralle, D. Fuhrer, Somatostatin receptor subtype expression in human thyroid tumours. Horm. Metab. Res 42(4), 237–240 (2010)CrossRefPubMed
10.
go back to reference H. Pisarek, T. Stepień, R. Kubiak, E. Borkowska, M. Pawlikowski, Expression of somatostatin receptor subtypes in human thyroid tumors: the immunohistochemical and molecular biology (RT-PCR) investigation. Thyroid Res 2(1), 1 (2009)CrossRefPubMedPubMedCentral H. Pisarek, T. Stepień, R. Kubiak, E. Borkowska, M. Pawlikowski, Expression of somatostatin receptor subtypes in human thyroid tumors: the immunohistochemical and molecular biology (RT-PCR) investigation. Thyroid Res 2(1), 1 (2009)CrossRefPubMedPubMedCentral
11.
go back to reference S. Sancak, A. Hardt, J. Singer, G. Klöppel, F.T. Eren, B.M. Güllüoglu et al. Somatostatin receptor 2 expression determined by immunohistochemistry in cold thyroid nodules exceeds that of hot thyroid nodules, papillary thyroid carcinoma, and Graves’ disease. Thyroid 20(5), 505–511 (2010)CrossRefPubMed S. Sancak, A. Hardt, J. Singer, G. Klöppel, F.T. Eren, B.M. Güllüoglu et al. Somatostatin receptor 2 expression determined by immunohistochemistry in cold thyroid nodules exceeds that of hot thyroid nodules, papillary thyroid carcinoma, and Graves’ disease. Thyroid 20(5), 505–511 (2010)CrossRefPubMed
12.
go back to reference G. Treglia, G. Rindi, V. Rufini, Expression of somatostatin receptors may guide the use of somatostatin receptor imaging and therapy in differentiated thyroid cancer. Hormones (Athens) 11(3), 230–232 (2012)CrossRefPubMed G. Treglia, G. Rindi, V. Rufini, Expression of somatostatin receptors may guide the use of somatostatin receptor imaging and therapy in differentiated thyroid cancer. Hormones (Athens) 11(3), 230–232 (2012)CrossRefPubMed
13.
go back to reference T. Lincke, J. Singer, R. Kluge, O. Sabri, R. Paschke, Relative quantification of indium-111 pentetreotide and gallium-68 DOTATOC uptake in the thyroid gland and association with thyroid pathologies. Thyroid 19(4), 381–389 (2009)CrossRefPubMed T. Lincke, J. Singer, R. Kluge, O. Sabri, R. Paschke, Relative quantification of indium-111 pentetreotide and gallium-68 DOTATOC uptake in the thyroid gland and association with thyroid pathologies. Thyroid 19(4), 381–389 (2009)CrossRefPubMed
14.
go back to reference G. Treglia, A. Tamburello, L. Giovanella, Detection rate of somatostatin receptor PET in patients with recurrent medullary thyroid carcinoma: a systematic review and a meta-analysis. Hormones (Athens) 16(4), 362–372 (2017)PubMed G. Treglia, A. Tamburello, L. Giovanella, Detection rate of somatostatin receptor PET in patients with recurrent medullary thyroid carcinoma: a systematic review and a meta-analysis. Hormones (Athens) 16(4), 362–372 (2017)PubMed
15.
go back to reference J.D. Kohlenberg, A. Panda, G.B. Johnson, M.R. Castro, Radiologic and clinicopathologic characteristics of thyroid nodules with focal 68Ga-DOTATATE PET activity. Nucl. Med. Commun. 42(5), 510–516 (2021)CrossRefPubMed J.D. Kohlenberg, A. Panda, G.B. Johnson, M.R. Castro, Radiologic and clinicopathologic characteristics of thyroid nodules with focal 68Ga-DOTATATE PET activity. Nucl. Med. Commun. 42(5), 510–516 (2021)CrossRefPubMed
16.
go back to reference J. Kunikowska, R. Matyskiel, P. Pawliszak, A. Zemczak, D. Pawlak, M. Plazinska et al. Analysis of additional 68Ga-DOTATATE thyroid uptake in patients with neuroendocrine tumors. Eur. J. Nucl. Med. Mol. Imaging 40, S479 (2013) J. Kunikowska, R. Matyskiel, P. Pawliszak, A. Zemczak, D. Pawlak, M. Plazinska et al. Analysis of additional 68Ga-DOTATATE thyroid uptake in patients with neuroendocrine tumors. Eur. J. Nucl. Med. Mol. Imaging 40, S479 (2013)
17.
go back to reference T. Lincke, G. Orschekowski, J. Singer, O. Sabri, R. Paschke, Increased Gallium-68 DOTATOC uptake in normal thyroid glands. Horm. Metab. Res. 43(4), 282–286 (2011)CrossRefPubMed T. Lincke, G. Orschekowski, J. Singer, O. Sabri, R. Paschke, Increased Gallium-68 DOTATOC uptake in normal thyroid glands. Horm. Metab. Res. 43(4), 282–286 (2011)CrossRefPubMed
18.
go back to reference P. Nockel, C. Millo, X. Keutgen, J. Klubo-Gwiezdzinska, J. Shell, D. Patel et al. The rate and clinical significance of incidental thyroid uptake as detected by Gallium-68 DOTATATE positron emission tomography/computed tomography. Thyroid 26(6), 831–835 (2016)CrossRefPubMedPubMedCentral P. Nockel, C. Millo, X. Keutgen, J. Klubo-Gwiezdzinska, J. Shell, D. Patel et al. The rate and clinical significance of incidental thyroid uptake as detected by Gallium-68 DOTATATE positron emission tomography/computed tomography. Thyroid 26(6), 831–835 (2016)CrossRefPubMedPubMedCentral
19.
go back to reference J. Singer, T. Lincke, O. Sabri, R. Paschke, Ga-68-Dotatoc P.E.T. detects a basal somatostatin receptor expression in normal, nodular, and goitrous thyroid glands. Thyroid 17, S102 (2007) J. Singer, T. Lincke, O. Sabri, R. Paschke, Ga-68-Dotatoc P.E.T. detects a basal somatostatin receptor expression in normal, nodular, and goitrous thyroid glands. Thyroid 17, S102 (2007)
20.
go back to reference M.C. Kreissl, F.A. Verburg, M.C. Hategan, R. Lorenz, J. Biko, I. Israel et al. Assessment of somatostatin receptor expression in advanced follicular thyroid cancer using Ga-68-DOTATOC-PET. Eur. J. Nucl. Med. Mol. Imaging 37, S290 (2010) M.C. Kreissl, F.A. Verburg, M.C. Hategan, R. Lorenz, J. Biko, I. Israel et al. Assessment of somatostatin receptor expression in advanced follicular thyroid cancer using Ga-68-DOTATOC-PET. Eur. J. Nucl. Med. Mol. Imaging 37, S290 (2010)
21.
go back to reference D. Putzer, A.K. Ross, M.G. Abriel, D. Kendler, G. Dobrozemsky, R. Bale et al. 68Ga-DOTA-Tyr3-octreotide PET in thyroid cancer patients compared to 18F-FDG-PET and radioiodine-avidity. Eur. J. Nucl. Med. Mol. Imaging 37, S214 (2010) D. Putzer, A.K. Ross, M.G. Abriel, D. Kendler, G. Dobrozemsky, R. Bale et al. 68Ga-DOTA-Tyr3-octreotide PET in thyroid cancer patients compared to 18F-FDG-PET and radioiodine-avidity. Eur. J. Nucl. Med. Mol. Imaging 37, S214 (2010)
22.
go back to reference E. Demirci, L. Kabasakal, M. Ocak, A. Aygun, M. Halac, B. Kanmaz, Evaluation of 68Ga-DOTA-TATE and68Ga-DOTA-NOC PET/CT in patients with differentiated thyroid cancer. Eur. J. Nucl. Med. Mol. Imaging 39, S404 (2012) E. Demirci, L. Kabasakal, M. Ocak, A. Aygun, M. Halac, B. Kanmaz, Evaluation of 68Ga-DOTA-TATE and68Ga-DOTA-NOC PET/CT in patients with differentiated thyroid cancer. Eur. J. Nucl. Med. Mol. Imaging 39, S404 (2012)
23.
go back to reference M. Ocak, E. Demirci, L. Kabasakal, A. Aygun, R.O. Tutar, A. Araman et al. Evaluation and comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET/CT imaging in well-differentiated thyroid cancer. Nucl. Med. Commun. 34(11), 1084–1089 (2013)CrossRefPubMed M. Ocak, E. Demirci, L. Kabasakal, A. Aygun, R.O. Tutar, A. Araman et al. Evaluation and comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET/CT imaging in well-differentiated thyroid cancer. Nucl. Med. Commun. 34(11), 1084–1089 (2013)CrossRefPubMed
24.
go back to reference S. Li, F. Wang, X. Yao, R. Liu, L. Zhang, 68Ga-DOTA-NOC and 18F-FDG PET/CT for the diagnosis of Iodine-refractory differentiated thyroid cancer : Pilot studies. Eur. J. Nucl. Med. Mol. Imaging 44(2), S650–S651 (2017) S. Li, F. Wang, X. Yao, R. Liu, L. Zhang, 68Ga-DOTA-NOC and 18F-FDG PET/CT for the diagnosis of Iodine-refractory differentiated thyroid cancer : Pilot studies. Eur. J. Nucl. Med. Mol. Imaging 44(2), S650–S651 (2017)
25.
go back to reference B. Vatankulu, B. Akovali, S. Saǧer, M. Halaç, L. Kabasakal, K. Sönmezoǧlu, 68Ga-DOTA-TATE PET-CT in differentiated thyroid cancer patients: Comparison with 18F-FDG PET-CT. Eur. J. Nucl. Med. Mol. Imaging 43(1), S223 (2016) B. Vatankulu, B. Akovali, S. Saǧer, M. Halaç, L. Kabasakal, K. Sönmezoǧlu, 68Ga-DOTA-TATE PET-CT in differentiated thyroid cancer patients: Comparison with 18F-FDG PET-CT. Eur. J. Nucl. Med. Mol. Imaging 43(1), S223 (2016)
26.
go back to reference I. Binse, T.D. Poeppel, M. Ruhlmann, S. Ezziddin, R. Görges, A. Sabet et al. 68Ga-DOTATOC PET/CT in patients with iodine- and 18F-FDG-negative differentiated thyroid carcinoma and elevated serum thyroglobulin. J. Nucl. Med. 57(10), 1512–1517 (2016)CrossRefPubMed I. Binse, T.D. Poeppel, M. Ruhlmann, S. Ezziddin, R. Görges, A. Sabet et al. 68Ga-DOTATOC PET/CT in patients with iodine- and 18F-FDG-negative differentiated thyroid carcinoma and elevated serum thyroglobulin. J. Nucl. Med. 57(10), 1512–1517 (2016)CrossRefPubMed
27.
go back to reference L.S. Almeida, M.C. Araújo, D.E. Zantut-Wittmann, L.V. Assumpção, T.F. Souza, C.M. Silva et al. Effect of thyroid-stimulating hormone in 68Ga-DOTATATE PET/CT of radioiodine-refractory thyroid carcinoma: a pilot study. Nucl. Med. Commun. 39(5), 441–450 (2018)CrossRefPubMed L.S. Almeida, M.C. Araújo, D.E. Zantut-Wittmann, L.V. Assumpção, T.F. Souza, C.M. Silva et al. Effect of thyroid-stimulating hormone in 68Ga-DOTATATE PET/CT of radioiodine-refractory thyroid carcinoma: a pilot study. Nucl. Med. Commun. 39(5), 441–450 (2018)CrossRefPubMed
28.
go back to reference M. Theodoropoulou, G.K. Stalla, Somatostatin receptors: from signaling to clinical practice. Front Neuroendocrinol. 34(3), 228–252 (2013)CrossRefPubMed M. Theodoropoulou, G.K. Stalla, Somatostatin receptors: from signaling to clinical practice. Front Neuroendocrinol. 34(3), 228–252 (2013)CrossRefPubMed
29.
go back to reference A. Gillis, R. Zheng-Pywell, C. McLeod, D. Wang, J.M. Ness, R. Guenter et al. Somatostatin receptor type 2 and thyroid-stimulating hormone receptor expression in oncocytic thyroid neoplasms: implications for prognosis and treatment. Mod. Pathol. 36(12), 100332 (2023)CrossRefPubMed A. Gillis, R. Zheng-Pywell, C. McLeod, D. Wang, J.M. Ness, R. Guenter et al. Somatostatin receptor type 2 and thyroid-stimulating hormone receptor expression in oncocytic thyroid neoplasms: implications for prognosis and treatment. Mod. Pathol. 36(12), 100332 (2023)CrossRefPubMed
30.
go back to reference S. Singh, R.K. Somvanshi, V. Panda, U. Kumar, Comparative distribution of somatostatin and somatostatin receptors in PTU-induced hypothyroidism. Endocrine 70(1), 92–106 (2020)CrossRefPubMed S. Singh, R.K. Somvanshi, V. Panda, U. Kumar, Comparative distribution of somatostatin and somatostatin receptors in PTU-induced hypothyroidism. Endocrine 70(1), 92–106 (2020)CrossRefPubMed
31.
go back to reference D.M. Carmona Matos, S. Jang, B. Hijaz, A.W. Chang, R.V. Lloyd, H. Chen et al. Characterization of somatostatin receptors (SSTRs) expression and antiproliferative effect of somatostatin analogues in aggressive thyroid cancers. Surgery 165(1), 64–68 (2019)CrossRefPubMed D.M. Carmona Matos, S. Jang, B. Hijaz, A.W. Chang, R.V. Lloyd, H. Chen et al. Characterization of somatostatin receptors (SSTRs) expression and antiproliferative effect of somatostatin analogues in aggressive thyroid cancers. Surgery 165(1), 64–68 (2019)CrossRefPubMed
32.
go back to reference Y. Sanli, I. Garg, A. Kandathil, T. Kendi, M.J.B. Zanetti, S. Kuyumcu et al. Neuroendocrine tumor diagnosis and management. AJR Am. J. Roentgenol. 211(2), 267–277 (2018)CrossRef Y. Sanli, I. Garg, A. Kandathil, T. Kendi, M.J.B. Zanetti, S. Kuyumcu et al. Neuroendocrine tumor diagnosis and management. AJR Am. J. Roentgenol. 211(2), 267–277 (2018)CrossRef
34.
go back to reference P. Oliván-Sasot, M. Falgás-Lacueva, J. García-Sánchez, V. Vera-Pinto, C. Olivas-Arroyo, P. Bello-Arques, Use of. Rev. Esp. Med Nucl. Imagen Mol. 36(2), 116–119 (2017)PubMed P. Oliván-Sasot, M. Falgás-Lacueva, J. García-Sánchez, V. Vera-Pinto, C. Olivas-Arroyo, P. Bello-Arques, Use of. Rev. Esp. Med Nucl. Imagen Mol. 36(2), 116–119 (2017)PubMed
35.
go back to reference S. Gubbi, M. Al-Jundi, J. Del Rivero, A. Jha, M. Knue, J. Zou et al. Case report: primary hypothyroidism associated with lutetium 177-DOTATATE therapy for metastatic paraganglioma. Front Endocrinol. (Lausanne) 11, 587065 (2020)CrossRefPubMed S. Gubbi, M. Al-Jundi, J. Del Rivero, A. Jha, M. Knue, J. Zou et al. Case report: primary hypothyroidism associated with lutetium 177-DOTATATE therapy for metastatic paraganglioma. Front Endocrinol. (Lausanne) 11, 587065 (2020)CrossRefPubMed
Metadata
Title
Somatostatin receptor imaging of thyroid tissue and differentiated thyroid cancer using gallium-68-labeled radiotracers—a review of clinical studies
Authors
Reza Pishdad
Giorgio Treglia
Ami Mehta
Prasanna Santhanam
Publication date
18-03-2024
Publisher
Springer US
Published in
Endocrine
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-024-03779-3
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