FAP inhibitors: are we really using the best method to evaluate the residence time?

Fibroblast activation protein inhibitors (FAPIs) have revolutionized molecular imaging, particularly with the development of PET tracers targeting the tumor microenvironment [1]. These tracers exploit the overexpression of FAP on cancer-associated fibroblasts (CAFs), enabling highly specific imaging of tumors with strong stromal activity. PET/FDG imaging plays a crucial role in cancer diagnosis, staging, and monitoring treatment response, providing valuable insights into metabolic activity and tumor progression [2, 3]. FAPI-based PET tracers, such as 68Ga-FAPI, offer superior diagnostic performance over conventional FDG-PET in various malignancies, including those with low glucose metabolism. Their ability to provide high tumor-to-background contrast has expanded their clinical applications to detect challenging primary and metastatic lesions [4]. With ongoing advancements, FAPI-PET tracers are poised to enhance both diagnostic precision and theranostic strategies in oncology. Despite their promising potential, FAPI-based PET tracers face limitations, including variable tumor uptake, rapid tracer washout in certain conditions and potential off-target activity in non-malignant processes such as inflammation or fibrosis, which can complicate diagnostic specificity [5].