PET/CT with Fibroblast Activation Protein Inhibitors in Breast Cancer: Diagnostic and Theranostic Application—A Literature Review

Simple Summary The fibroblast activation protein (FAP) is highly expressed on cancer-associated fibroblasts in many tumors. Radiolabeled FAP inhibitors (FAPIs) have been recently developed as new promising radiotracers in an oncological setting, both as diagnostic imaging by Positron Emission Tomography/Computed Tomography (PET/CT) and as new anti-cancer treatment, in a theranostic perspective. This narrative review aimed to summarize the current evidence on the role of FAPI radiotracers in the diagnostic and therapeutic management of patients with breast cancer (BC). Despite some clinical and methodological heterogeneity among the evaluated studies, Ga-68-FAPI PET/CT emerges as a valuable diagnostic tool in BC patients, demonstrating a general high tumor uptake across all histological and molecular BC subtypes, along with technical advantages and an overall better performance than the standard-of-care F-18-FDG. Moreover, although with still limited clinical evidence, treatment with radiolabeled FAPIs seems a promising approach in BC patients, increasing the possibility of more personalized treatments. Growing studies have recently reported on the promising application of radiolabeled-fibroblast activation protein inhibitors (FAPIs) as diagnostic and therapeutic agents in various oncological populations. To exclusively evaluate the current evidence on the diagnostic and therapeutic role of FAPI radiotracers in patients with breast cancer (BC), a narrative review of the available literature was performed. A search algorithm from PubMed/MEDLINE, based on the combination of "PET" OR "positron emission tomography" and "FAPI" and "cancer", with a last update in February 2022, was applied. From 233 identified articles, 33 studies conducted in BC patients and with available data on PET imaging or radiolabeled-FAPI therapy were finally considered, for a total of 191 patients. Despite some clinical and methodological heterogeneity among the reviewed articles, Ga-68-FAPI PET/CT emerges as a valuable diagnostic tool in BC patients both at staging and restaging, also demonstrating several technical advantages and an overall better performance than F-18-FDG, especially in histotypes with well-known low F-18-FDG avidity. Moreover, although with still limited clinical evidence in BC, radiolabeled FAPIs emerge as promising therapeutic agents in a theranostic perspective, increasing the possibility of more personalized treatments. From these results, future research directions on FAPI radiotracers application in BC patients are suggested.