Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer

SIMPLE SUMMARY: Radioiodine therapy is the main treatment option for metastatic differentiated thyroid cancer (DTC). However, only half of these patients achieve (partial or complete) remission or have stable disease during long-term follow-up. In the remaining ones, disease progresses mainly as they become radioiodine-refractory. The diagnostics of radioiodine-refractory disease are extensively debated. The introduction of novel tracers besides radioiodine isotopes ((131)I, (123)I, and (124)I) and 2-[(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) opens new options for the diagnostics and therapy of this subgroup of DTC patients. Prostate-specific membrane antigen (PSMA) ligands, fibroblast activation protein inhibitors (FAPI), and somatostatin receptor-targeted radiopharmaceuticals appear to be new potential theranostics tracers. In this review, we will elaborate on the role of these radiopharmaceuticals in the management of radioiodine-refractory disease. ABSTRACT: Differentiated thyroid cancer (DTC) is the most common subtype of thyroid cancer and has an excellent overall prognosis. However, metastatic DTC in certain cases may have a poor prognosis as it becomes radioiodine-refractory. Molecular imaging is essential for disease evaluation and further management. The most commonly used tracers are [(18)F]FDG and isotopes of radioiodine. Several other radiopharmaceuticals may be used as well, with different diagnostic performances. This review article aims to summarize radiopharmaceuticals used in patients with radioiodine-refractory DTC (RAI-R DTC), focusing on their different molecular pathways. Additionally, it will demonstrate possible applications of the theranostics approach to this subgroup of metastatic DTC.