Multi-Tracer PET-Guided Therapy Selection and Theranostics in Radioiodine-Refractory Thyroid Cancer Patient Unsuitable for Tyrosine Kinase Inhibitor Therapy

Abstract

Radioactive iodine refractory (RAIR) thyroid cancer and thyroglobulin elevated negative iodine scintigraphy constitute a fraction of thyroid cancer patients with poorer prognosis as opposed to radioiodine concentrating disease. Although not a rare condition and with several treatment options already explored, the selection of an optimal therapy that balances effective disease stabilization, symptom palliation, life prolongation, and minimal side effects remains essential. The use of multi-tracer positron emission tomography (PET) shows potential for radionuclide therapy selection in RAIR thyroid cancer. In this case report, multi-tracer PET imaging was employed to assess the feasibility of available theranostic options. While [⁶⁸Ga]Ga-DOTATATE PET/computed tomography (CT) showed low-level somatostatin receptor expression, [⁶⁸Ga]Ga-prostate specific membrane antigen (PSMA)-11 PET/CT revealed moderate and concordant PSMA expression across all lesions observed on [¹⁸F]F-FDG PET/CT, justifying [¹⁷⁷Lu]Lu-PSMA-617 therapy in this patient.

Keywords

radioiodine-refractory thyroid cancer - multi-tracer PET/CT - theranostics - targeted radionuclide therapy - molecular imaging - PET-guided treatment planning

Publication History

Article published online:
04 October 2025

• References

• 1 Haugen BR, Alexander EK, Bible KC. 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 2016; 26 (01) 1-133
• 2 de Vries LH, Lodewijk L, Braat AJAT. et al. ⁶⁸Ga-PSMA PET/CT in radioactive iodine-refractory differentiated thyroid cancer and first treatment results with ¹⁷⁷Lu-PSMA-617. EJNMMI Res 2020; 10 (01) 18
• 3 Durante C, Haddy N, Baudin E. et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 2006; 91 (08) 2892-2899
• 4 Schlumberger M, Tahara M, Wirth LJ. et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015; 372 (07) 621-630
• 5 Brose MS, Nutting CM, Jarzab B. et al. Sorafenib in locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. Lancet 2014; 384 (9940): 319-328
• 6 Strosberg J, El-Haddad G, Wolin E. et al; NETTER-1 Trial Investigators. Phase 3 trial of ¹⁷⁷Lu-DOTATATE for midgut neuroendocrine tumors. N Engl J Med 2017; 376 (02) 125-135
• 7 Sartor O, de Bono J, Chi KN. et al; VISION Investigators. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med 2021; 385 (12) 1091-1103
• 8 Hofman MS, Violet J, Hicks RJ. et al. [¹⁷⁷Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol 2018; 19 (06) 825-833
• 9 Bychkov A, Vutrapongwatana U, Tepmongkol S, Keelawat S. PSMA expression by microvasculature of thyroid tumors - potential implications for PSMA theranostics. Sci Rep 2017; 7 (01) 5202
• 10 Assadi M, Ahmadzadehfar H. ¹⁷⁷Lu-DOTATATE and ¹⁷⁷Lu-prostate-specific membrane antigen therapy in a patient with advanced metastatic radioiodine-refractory differentiated thyroid cancer after failure of tyrosine kinase inhibitors treatment. World J Nucl Med 2019; 18 (04) 406-408
• 11 Verma P, Malhotra G, Meshram V. et al. Prostate-specific membrane antigen expression in patients with differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy using 68Ga-PSMA-HBED-CC PET/CT. Clin Nucl Med 2021; 46 (08) e406-e409