High fibroblast-activation-protein expression in castration-resistant prostate cancer supports the use of FAPI-molecular theranostics

Abstract

Purpose To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [68 Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC). Methods Tissue microarrays (TMAs) were constructed from prostatic tissue from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and neuroendocrine PC (NEPC)) and were stained with anti-FAP monoclonal antibody. A positive pixel count algorithm (H-Index) was used to compare FAP expression between the groups. Additionally, three men with advanced CRPC or NEPC underwent [68 Ga]Ga-FAPI-04 PET/CT, and PET positivity was analyzed. Results The mean H-index for benign tissue, primary PC, neoadjuvant androgen deprivation therapy before radical prostatectomy, CRPC, and NEPC was 0.018, 0.031, 0.042, 0.076, and 0.051, respectively, indicating a significant rise in FAP expression with advancement of disease. Corroborating these findings [68 Ga]Ga-FAPI-04 PET/CT was highly positive in men with advanced CRPC. Conclusion Increased FAP tissue expression supports the use of FAP inhibitor (FAPI)-molecular theranostics in CRPC.

Potential Targets Other Than PSMA for Prostate Cancer Theranostics: A Systematic Review

“…Fibroblast activation protein inhibitors (FAPis) are quinoline-based inhibitors that have recently been radiolabeled with gallium-68 for PET imaging of various cancers, including CaP, in 2 studies [ 55 , 56 ]. FAP expression by PCa cells assessed by [ 68 Ga]Ga-FAPI-04 PET uptake is reported to be sufficient in mCRPC patients to consider the use of FAPI radiolabeled with a radionuclide suitable for therapy in those patients [ 68 ]. Such radiotracers are still in development for clinical use.…”

“…Radiolabeled FAPis are the most recent and promising molecules that have been developed and tested in multiple tumor types. They are believed to be sufficiently overexpressed in CRPC to perform RLT [ 68 ]. RLT with FAPis have recently been tested in humans but not in PCa [ 71 ].…”

Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival

“…Furthermore, PET imaging with a FAP-targeted antibody imaging probe, 89 Zr-B12 IgG, was successfully evaluated in preclinical PC models, demonstrating high tumor uptake and long-term retention of the probe [ 21 ]. Clinical evaluation of another PET-probe, 68 Ga-FAPI PET/CT demonstrated multiple metastatic lesions confirmed by conventional CT scan in three metastatic CRPC and NEPC patients, supporting the role of FAP as a key diagnostic target [ 19 ]. Interestingly, when 68 Ga-FAPI was compared head-to-head with 18 F-FDG PET/CT in a multicenter study of 71 patients with various primaries, the former had similar quantitative tumor uptake, but lower background uptake, yielding improved diagnostic information particularly in tumor areas with high physiological 18 F-FDG uptake [ 22 ].…”

“…A gradient of increasing FAP protein expression in prostate tissue microarrays (TMA) from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and NEPC) was recently reported, indicating a significant rise upon disease progression at the CRPC and NEPC states [ 19 ]. Our work complements these findings, by demonstrating that high FAP transcript levels are associated with worse prognosis of mCRPC patients.…”

FAPI PET/CT in the Diagnosis of Abdominal and Pelvic Tumors

“…The results revealed that FAP expression increased significantly with disease progression. In patients with advanced castration-resistant prostate cancer, 68 Ga-FAPI-04 PET/CT was highly positive ( 143 ). Other researchers found that FAP expression is significantly increased in metastatic disease compared with primary prostate cancer ( 144 ).…”