Title
Novel FAP-targeted Approach to Metastatic Prostate Cancer

Description
2.0 BACKGROUND
Despite recent breakthroughs in molecular imaging and theranostics, detection and treatment of the most aggressive metastatic castration resistant prostate cancer (CRPC) remain limited.1,2 The recent development of prostate-specific membrane antigen (PSMA)-directed imaging and therapy has made a significant impact on the lives of prostate cancer patients, mainly through (1) detection of recurrent/metastatic disease by PSMA-targeted positron emission tomography (PET),3–6 and (2) prolonging survival in CRPC patients through PSMA-targeted radioligand therapy (RLT).1 However, the vast majority of patients with CRPC relapse after response to PSMA-RLT, with an average increase in overall survival of 4 months, possibly due to suboptimal dosimetry, variable PSMA expression, and impact of tumor microenvironment.1 Hence, there is a critical unmet need for novel diagnostic and therapeutic interventions for these patients.

Fibroblast activation protein (FAP) is a cell-surface protease expressed by activated fibroblasts in various pathologic processes, such as by the cancer-associated fibroblasts in the tumor microenvironment. Radiolabeled FAP inhibitor (FAPI) agents have enabled PET imaging of a variety of cancers, including prostate cancer.7–10 However, utility of FAPI PET in diagnosis, staging, and management of prostate cancer is not fully investigated.

Objective
Primary:
Demonstrate the utility of FAPI PET in detection of metastatic prostate cancer
Secondary:
- Identify the clinical states & therapeutic associations of tumor FAPI uptake in metastatic prostate cancer.
- Evaluate whole-body diffusion weighted MR imaging in patients with prostate cancer.

Treatment The main objectives of this proposal are to (1) demonstrate the utility of FAPI PET in detection of metastatic prostate cancer, (2) establish the relationship between lesion FAPI uptake on PET and FAP expression at tissue level, and (3) identify the clinical state and therapeutic associations of tumor with FAPI PET.

Key Eligibility Eligibility Criteria:

Age 18 years or older

Able and willing to provide informed consent

Known diagnosis of prostate cancer with established or suspected non-osseous, non-nodal metastases. This pattern of metastatic disease is chosen as it is representative of those patients who harbor the more aggressive subtype of prostate cancer, among whom PSMA PET is likely to be negative.

Scheduled for standard-of-care (SOC) PSMA PET

Scheduled for SOC biopsy of an established or suspected non-osseous, non-nodal metastases.

Willing and able to undergo PET/MRI as part of this research

Applicable Disease Sites
Prostate

Participating Institutions
Wisconsin Institute for Medical Research (WIMR)