Comparison of Prostate-Specific Membrane Antigen Based F-18-DCFBC PET/CT to Conventional Imaging Modalities for Detection of Hormone-Naive and Castration-Resistant Metastatic Prostate Cancer

Conventional imaging modalities (CIMs) have limited sensitivity and specificity for detection of metastatic prostate cancer. We examined the potential of a first-in-class radiofluorinated small-molecule inhibitor of prostate-specific membrane antigen (PSMA), N-[N-[(S)-1,3-dicarboxypropyfIcarbamoyl]-4-F-18-fluorobenzyl-L-cysteine (F-18-DCFBC), to detect metastatic hormone-naive (HNPC) and castration-resistant prostate cancer (CRPC). Methods: Seventeen patients were prospectively enrolled (9 HNPC and 8 CRPC); 16 had CIM evidence of new or progressive metastatic prostate cancer and 1 had high clinical suspicion of metastatic disease. F-18-DCFBC PET/CT imaging was obtained with 2 successive PET scans starting at 2 h after injection. Patients were imaged with CIM at approximately the time of PET. A lesion-by-lesion analysis of PET to CIM was performed in the context of either HNPC or CRPC. The patients were followed with available clinical imaging as a reference standard to determine the true nature of identified lesions on PET and CIM. Results: On the lesion-by-lesion analysis, F-18-DCFBC PET was able to detect a larger number of lesions (592 positive with 63 equivocal) than CIM (520 positive with 61 equivocal) overall, in both HNPC and CRPC patients. F-18-DCFBC PET detection of lymph nodes, bone lesions, and visceral lesions was superior to CIM. When intrapatient clustering effects were considered, F-18-DCFBC PET was estimated to be positive in a large proportion of lesions that would be negative or equivocal on CIM (0.45). On follow-up, the sensitivity of F-18-DCFBC PET (0.92) was superior to CIM (0.71). 18F-DCFBC tumor uptake was increased at the later PET time point (similar to 2.5 h after injection), with background uptake showing a decreasing trend on later PET. Conclusion: PET imaging with F-18-DCFBC, a small-molecule PSMA-targeted radiotracer, detected more lesions than CIM and promises to diagnose and stage patients with metastatic prostate cancer more accurately than current imaging methods.