Diagnostic value of [99mTc]Tc-HYNIC-TOC scintigraphy in the management of differentiated thyroid cancer with elevated thyroglobulin and negative radioiodine whole-body scan

Document Type : Original Article

Authors

1 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Nuclear Medicine, Ultrasound and PET, Westmead Hospital, Sydney, Australia

Abstract

Introduction: Negative radioiodine (131I) whole-body scan with elevated serum thyroglobulin (Tg) level are found in 20% of patients with differentiated thyroid cancer (DTC), which can be a diagnostic challenge. We evaluated the efficacy of Technetium-99m-Hydrazinonicotinyl-Tyr3-Octreotide ([99mTc]Tc-HYNIC-TOC) somatostatin receptor scintigraphy (SRS) for detection of non-iodine-avid metastases and its impact on staging and management of these patients.
Methods: The study population consisted of 35 DTC patients (25 females; PTC = 88.2%, FTC = 11.8%) who had elevated serum Tg levels despite negative post-ablation radioiodine whole-body scan. All patients underwent whole body SRS 3-4 hours after intravenous injection of 20mCi (740 MBq) of [99mTc]Tc-HYNIC-TOC. Sites of suspected radiotracer accumulation were confirmed with anatomic imaging. Ultimately, corresponding changes in the staging and management were recorded.
Results: SRS was positive in 27 (77.1%) cases. Patients with positive scan had significantly higher Tg levels at the time of scan, compared to those with negative scans (154.5±188.6 vs. 28.2±32.7 ng/mL, p-value = 0.005). Interestingly, previous history of neck external beam radiation therapy (EBRT) was significantly correlated with [99mTc]Tc-HYNIC-TOC avidity (Likelihood ratio = 11.2, p = 0.005). Addition of SSTR scintigraphy changed overall staging and management in 11% and 32.4% of the patients, respectively.
Conclusion: SRS can be a useful diagnostic adjunct in DTC patients with highly elevated Tg and negative radioiodine whole-body scan. The likelihood of positive findings on [99mTc]Tc‑HYNIC‑TOC was higher in cases with previous history of EBRT or high Tg levels (i.e. suppressed-Tg >80 ng/mL) at the time of scan.

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References

  1. Fu H, Sa R, Cheng L, Jin Y, Qiu X, Liu M, Chen L. Updated review of nuclear molecular imaging of thyroid cancers. Endocr Pract. 2021 May;27(5):494-502.
  2. Asban A, Patel AJ, Reddy S, Wang T, Balentine CJ, Chen H. Cancer of the endrocrine system. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE. Abeloff's clinical oncology. 6th  ed. Philadelphia (PA): Elsevier; 2020. p.1074-76.
  3. American Cancer Society. Cancer Facts & Figures 2020. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed: Dec 19, 2021.
  4. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE. 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. 2016;26(1):1-133.
  5. Schlumberger M, Brose M, Elisei R, Leboulleux S, Luster M, Pitoia F. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol. 2014;2(5):356-58.
  6. Trybek T, Kowalska A, Lesiak J, Młynarczyk J. The role of 18F-Fluorodeoxyglucose Positron Emission Tomography in patients with suspected recurrence or metastatic differentiated thyroid carcinoma with elevated serum thyroglobulin and negative I-131 whole body scan. Nucl Med Rev 2014;17(2):87-93.
  7. Mu ZZ, Zhang X, Lin YS. Identification of Radioactive iodine refractory differentiated thyroid cancer. Chonnam Med J. 2019 Sep;55(3):127-135.
  8. Dionigi G, Fama' F, Pignata SA, Pino A, Pontin A, Caruso E, Fu Y, Li S, Mazzeo C, Sun H, Baldari S. Usefulness of PET-CT scan in recurrent thyroid cancer. World J Otorhinolaryngol Head Neck Surg. 2020 Jul 7;6(3):182-187.
  9. Mourato FA, Almeida MA, Brito AE, Leal AL, Almeida Filho P, Etchebehere E. FDG PET/CT versus somatostatin receptor PET/CT in TENIS syndrome: a systematic review and meta-analysis. Clin Transl Imaging. 2020;8:365-375.
  10. Sinha P, Conrad GR, West HC. Response of thyroglobulin to radioiodine therapy in thyroglobulin-elevated negative iodine scintigraphy (TENIS) syndrome. Anticancer Res. 2011;31(6):2109-12.
  11. Qichang W, Lin B, Gege Z, Youjia Z, Qingjie M, Renjie W, Bin J. Diagnostic performance of 2-[18F]FDG PET/CT in DTC patients with thyroglobulin elevation and negative iodine scintigraphy: a meta-analysis. Eur J Endocrinol. 2019 Aug 1;181(2):93-102.
  12. Nascimento C, Borget I, Al Ghuzlan A, Deandreis D, Hartl D, Lumbroso J. Postoperative fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography: an important imaging modality in patients with aggressive histology of differentiated thyroid cancer. Thyroid. 2015;25(4):437-44.
  13. Wang H, Dai H, Li Q, Shen G, Shi L, Tian R. Investigating 2-[18F]FDG PET/CT Parameters as Prognostic Markers for Differentiated Thyroid Cancer: A Systematic Review. Front Oncol. 2021 May 13;11:648658.
  14. Scott A, Boktor R, Lee ST, Berlangieri S. Impact of 2-[18F]FDG PET/CT on treatment of patients with differentiated thyroid carcinoma, negative 131I whole body scan and elevated serum thyroglobulin. Asia Oceania J Nucl Med Biol. 2022;10(1):20-27.
  15. Caetano R, Biz AN, Schluckebier LF, Silva RM, Braga JU, Bastos CR. Cost-effectiveness of the use of positron emission tomography in the detection of recurrence of differentiated thyroid cancer. Physis: Revista de Saúde Coletiva. 2016;26(1):331-356.
  16. Annunziata S, Caldarella C, Treglia G. Cost-effectiveness of Fluorine-18-Fluorodeoxyglucose positron emission tomography in tumours other than lung cancer: A systematic review. World J Radiol. 2014 Mar 28;6(3):48-55.
  17. Maghsoomi Z, Emami Z, Malboosbaf R, Malek M, Khamseh ME. Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review. BMC cancer. 2021 Dec;21(1):1-4.
  18. Korde A, Mallia M, Shinto A, Sarma H, Samuel G, Banerjee S. Improved kit formulation for preparation of [99mTc]Tc-HYNIC-TOC: Results of preliminary clinical evaluation in imaging patients with neuroendocrine tumors. Cancer Biother Radiopharm 2014;29(9):387-94.
  19. Jahanpanah P, Shakeri S, Kiamanesh Z, Nasiri Z, Aryana K. Detection of solitary bone metastasis by 99mTc-octreotide scintigraphy in a patient with Hurthle cell carcinoma: A case report. Iran J Nucl Med. 2020;28(1):48-50.
  20. Hofman MS, Lau WE, Hicks RJ. Somatostatin receptor imaging with 68Ga Dotatate PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 2015 Mar;35(2):500-16.
  21. Görges R, Kahaly G, Müller-Brand J, Mäcke H, Roser HW, Bockisch A. Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer. Thyroid. 2001;11(7):647-59.
  22. Valli N, Catargi B, Ronci N, Leccia F, Guyot M, Roger P, et al. Evaluation of indium-111 pentetreotide somatostatin receptor scintigraphy to detect recurrent thyroid carcinoma in patients with negative radioiodine scintigraphy. Thyroid. 1999;9(6):583-89.
  23. Haslinghuis L, Krenning E, De Herder W, Reijs A, Kwekkeboom D. Somatostatin receptor scintigraphy in the follow-up of patients with differentiated thyroid cancer. J Endocrinol Invest. 2001;24(6):415-22.
  24. Askari E, Aghaei A, Aryana K. Somatostatin receptor imaging and therapy in differentiated thyroid cancer: a ray of hope or the flash before total darkness? Clin Transl Imaging. 2021;9:275-276.
  25. Gabriel M, Froehlich F, Decristoforo C, Ensinger C, Donnemiller E, von Guggenberg E. [99mTc]Tc-EDDA/HYNIC-TOC and 2-[18F]FDG in thyroid cancer patients with negative 131 I whole-body scans. Eur J Nucl Med. 2004;31(3):330-41.
  26. Parisella M, D'Alessandria C, van de Bossche B, Chianelli M, Ronga G, Papini E. [99mTc]Tc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma. Cancer Biother. Radiopharm. 2004;19(2):211-17.
  27. Czepczyński R, Kosowicz J, Ziemnicka K, Mikołajczak R, Gryczyńska M, Sowiński J. The role of scintigraphy with the use of [99mTc]Tc-HYNIC-TOC in the diagnosis of medullary thyroid carcinoma. Endokrynol Pol. 2006;57(4):431-37.
  28. Shinto AS, Kamaleshwaran K, Mallia M, Korde A, Samuel G, Banerjee S. Utility of [99mTc]Tc-HYNIC-TOC in 131I whole-body scan negative thyroid cancer patients with elevated serum thyroglobulin levels. World J Nucl Med. 2015;14(2):101-8.
  29. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):569.
  30. Ortega J, Sala C, Flor B, Lledo S. Efficacy and cost-effectiveness of the UltraCision® harmonic scalpel in thyroid surgery: an analysis of 200 cases in a randomized trial. J Laparoendosc Adv Surg Tech A. 2004 Feb;14(1):9-12.
  31. Rahbari R, Zhang L, Kebebew E. Thyroid cancer gender disparity. Future Oncol. 2010;6(11):1771-79.
  32. Czepczyński R, Gryczyńska M, Ruchała M. [99mTc]Tc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment. Nucl Med Rev. 2016;19(2):67-73.
  33. Shakeri S, Jahanpanah P, Divband G, Massoudi T, Aryana K. 99m Tc-Octreotide-avid brain mass in a patient with poorly differentiated papillary thyroid carcinoma, hope in despair. Nucl Med Rev. 2020;23(1):49-50.
  34. Garin E, Devillers A, Le Cloirec J, Bernard A, Lescouarc’h J, Herry J. Use of indium-111 pentetreotide somatostatin receptor scintigraphy to detect recurrent thyroid carcinoma in patients without detectable iodine uptake. Eur J Nucl Med. 1998;25(7):687-94.
  35. Woodmansee WW, Gordon DF, Dowding JM, Stolz B, Lloyd RV, James RA. The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors. Thyroid. 2000;10(7):533-41.
  36. Lee DY, Kim YI. Peptide receptor radionuclide therapy in patients with differentiated thyroid cancer: a meta-analysis. Clin Nucl Med. 2020 Aug 1;45(8):604-10.

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