FAPi-Based Agents in Thyroid Cancer: A New Step towards Diagnosis and Therapy? A Systematic Review of the Literature

Simple Summary The main topic of this present paper is an analysis of the performance of FAPi agents in cases of thyroid cancer, both in diagnosis and therapy. Up to 50% of instances of thyroid cancer lose their avidity to 131I and become more aggressive. In this scenario, [18F]FDG PET/CT is used for evaluating the widespread nature of the disease, despite its low sensitivity. FAPi agents represent a promising novel class of tracers and a valid alternative to [18F]FDG and 131I scans. They also represent a thriving future perspective in theranostics. This systematic review aims to examine and discuss the advantages and pitfalls of FAPi agents presented in the literature in the context of the diagnosis and treatment of thyroid cancer.Abstract (1) Background: Thyroid cancer (TC) is often treated with surgery followed by iodine-131. Up to 50% of the instances of TC lose their avidity to 131I, becoming more aggressive. In this scenario, [18F]FDG PET/CT imaging is used for evaluating the widespread nature of the disease, despite its low sensitivity and a false negative rate of 8-21.1%. A novel class of PET agents targeting the fibroblast activation protein inhibitor (FAPi) has emerged, studied particularly for their potential application to theranostics. (2) Methods: A search of the literature was performed by two independent authors (P.G. and L.E.) using the PubMed, Scopus, Web of Science, Cochrane Library, and EMBASE databases. The following terms were used: "FAP" or "FAPi" or "Fibroblast activating protein" and "thyroid" or "thyroid cancer", in different combinations. The included papers were original articles, clinical studies, and case reports in the English language. No time limits were used. Editorials, conference papers, reviews, and preclinical studies were excluded. (3) Results: There were 31 papers that were selected. Some studies reported a low or absent FAPi uptake in TC lesions; others reported promising findings for the detection of metastases. (4) Conclusions: The preliminary results are encouraging. FAPI agents are an alternative to [18F]FDG and a promising theranostic tool. However, further studies with a larger population are needed.