Current and Emerging Radiotracers and Technologies for Detection of Advanced Differentiated Thyroid Cancer: A Narrative Review

Advanced differentiated thyroid cancer (DTC) presents diagnostic challenges, especially in cases refractory to conventional therapies. This review explores emerging radiotracers and imaging technologies designed to enhance diagnostic accuracy and therapeutic decision-making. Iodine-based radiopharmaceuticals, including I-123, I-131, and I-124 PET/CT, remain essential for detecting radioiodine-avid DTC, leveraging sodium-iodide symporter (NIS) expression. However, heterogeneity in NIS functionality often limits their effectiveness. Novel agents like [18F] FSO3 and [18F] TFB show promise in improving molecular imaging specificity. For radioiodine-refractory DTC (RAI-R), 18F-FDG PET/CT remains the cornerstone, aiding in disease localization, therapy monitoring, and prognosis. Emerging modalities, such as 68Ga-DOTA-based agents targeting somatostatin receptors (SSTR) and 68Ga-FAPI for fibroblast activation protein imaging, offer high sensitivity for poorly differentiated lesions and metastatic disease. Additionally, PSMA- and RGD-based imaging provide unique avenues for theranostic applications by targeting tumor neovascularization and integrin expression. The integration of nanotechnology, theranostic principles, and advanced imaging probes continues to evolve, enabling personalized approaches to DTC management. By summarizing these advancements, this review underscores the growing potential of molecular imaging and theranostics in addressing the unmet needs of advanced and refractory DTC.