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 (131I, 123I, and 124I) and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]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 [18F]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.