Clinical and research applications of fibroblast activation protein-α inhibitor tracers: a review

In the last decade, fibroblast activation protein-α inhibitors (FAPIs), which target the cancer-associated fibroblasts of the tumour microenvironment, have become a topic of great interest. In oncology, FAPI PET/CT imaging has repeatedly demonstrated a higher lesion detection rate than other conventional imaging modalities such as CT or 18F-FDG PET/CT for several tumours. In some cases, the initial staging and therapeutic management may even change. Some FAPI radioligands may also be labelled with therapeutic radionuclides for theranostic applications. It is thus possible to treat certain metastatic cancers with FAPI radioligand therapy (FAPI-RLT), which is generally well tolerated with little toxicity. Recently, new FAPIs have been developed with the particularity of having a higher binding affinity for the target, which further improves the lesion detection rate on PET/CT and clinical outcomes following FAPI-RLT. This review provides recent updates in the clinical use of FAPI PET/CT and FAPI-RLT and discusses potential emergent applications, including in inflammation imaging.