<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [<jats:sup>68</jats:sup> Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC).</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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 [<jats:sup>68</jats:sup> Ga]Ga-FAPI-04 PET/CT, and PET positivity was analyzed.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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 [<jats:sup>68</jats:sup> Ga]Ga-FAPI-04 PET/CT was highly positive in men with advanced CRPC.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Increased FAP tissue expression supports the use of FAP inhibitor (FAPI)-molecular theranostics in CRPC.</jats:p> </jats:sec>