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

Abstract

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-dicarboxypropyl]carbamoyl]-4-18F-fluorobenzyl-l-cysteine (18F-DCFBC), to detect metastatic hormone-naïve (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. 18F-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, 18F-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. 18F-DCFBC PET detection of lymph nodes, bone lesions, and visceral lesions was superior to CIM. When intrapatient clustering effects were considered, 18F-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 18F-DCFBC PET (0.92) was superior to CIM (0.71). 18F-DCFBC tumor uptake was increased at the later PET time point (∼2.5 h after injection), with background uptake showing a decreasing trend on later PET. Conclusion PET imaging with 18F-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.

PSMA Ligands for PET Imaging of Prostate Cancer

“…In metastatic PC patients, the diagnostic performance of both 18 F-DCFBC and 18 F-DCFPyL PET/CT was superior to that of standard-of-care imaging for detecting suggestive lesions (32,43). In a head-to-head comparison in 14 patients with recurrent PC, staging with 18 F-DCFPyL PET/CT was equivalent to that with 68 Ga-PSMA-11 (44).…”

(2S)-2-(3-(1-Carboxy-5-(4-211At-Astatobenzamido)Pentyl)Ureido)-Pentanedioic Acid for PSMA-Targeted α-Particle Radiopharmaceutical Therapy

“…211 At-6 is in a class of urea-based small molecules that targets PSMA and have shown uptake in pelvic and paraaortic lymph node metastases, prostate, visceral metastases, and bone metastases in human PC imaging studies (9,10). Accordingly, PSMAtargeted a-particle RPT may be suitable for any PC site, particularly for micrometastatic disease not visible by imaging.…”

“…To expand beyond the success of Xofigo, we developed 211 At-6, a urea-based a-emitter that targets prostate-specific membrane antigen (PSMA), which is overexpressed more than 1,000-fold relative to normal prostate in nearly all PC and is present in solid tumor neovasculature (6)(7)(8). On the basis of clinical studies with PSMA-targeted imaging agents (9,10), both bone and softtissue metastases should be treatable by targeting PSMA. Moreover, the perinuclear localization of PSMA enhances tumor cell kill (11).…”

Glu-Ureido–Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic Radiotracers

“…The clinical potential of this novel PSMA-targeted PET radioligand is currently being explored (29,30). The 18 F-labeled PET radioligands (31)(32)(33) and DCFPyL ( 18 F-DCFPyL) (34,35) were recently introduced into clinical settings as well. In contrast, 18 F-PSMA-1007 has the advantage that tracer-associated activity accumulation in the urinary bladder over time is almost not observable; this advantage makes this 18 F-labeled PSMA radioligand an ideal candidate for the primary diagnosis of PC and the staging of local recurrent disease (29,30).…”