FAP and PSMA Expression by Immunohistochemistry and PET Imaging in Castration-Resistant Prostate Cancer: A...

Area of Science:

• Oncology
• Molecular Imaging
• Cancer Biology

Background:

• Prostate-specific membrane antigen (PSMA) is a key theranostic target for metastatic prostate cancer (PCa).
• Castration-resistant prostate cancer (CRPC) can lose PSMA expression post-therapy, necessitating alternative targets.
• Fibroblast activation protein (FAP), found in cancer-associated fibroblasts, is a potential alternative target in PCa.

Purpose of the Study:

• To evaluate fibroblast activation protein (FAP) expression in castration-resistant prostate cancer (CRPC).
• To compare FAP expression with prostate-specific membrane antigen (PSMA) expression in CRPC.
• To assess the potential of FAP-targeted imaging in CRPC.

Main Methods:

• Immunohistochemistry assessed FAP expression in 116 CRPC tumors across different subtypes.
• Manual and automated scoring of FAP expression were correlated.
• Paired FAP and PSMA staining analyzed in CRPC tissue microarrays (n=62).
• Preliminary analysis of 4 patients from a [68Ga]-FAPi-46 PET imaging trial.

Main Results:

• FAP expression in CRPC was significantly lower than PSMA expression (median immunoscores 14 vs. 72).
• FAP expression was comparable across CRPC histologic subtypes, unlike PSMA.
• Among PSMA-negative tumors (19), 58% showed FAP positivity.
• FAPi PET imaging showed lower uptake than PSMA PET in clinical trial patients, correlating with lower FAP expression.

Conclusions:

• Low FAP expression levels in CRPC may limit the utility of FAP inhibitor (FAPi) PET imaging.
• FAPi PET imaging could be explored for PSMA-negative CRPC, including small cell carcinoma.
• Alternative molecular imaging modalities should be investigated for CRPC.