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-(18)F-fluorobenzyl-l-cysteine ((18)F-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. (18)F-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, (18)F-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. (18)F-DCFBC PET detection of lymph nodes, bone lesions, and visceral lesions was superior to CIM. When intrapatient clustering effects were considered, (18)F-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 (18)F-DCFBC PET (0.92) was superior to CIM (0.71). (18)F-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 (18)F-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.

Keywords: bone scan; computed tomography; metastatic prostate cancer; positron emission tomography; prostate-specific membrane antigen.

Figure 1

Chemical structure of ¹⁸F-DCBFC, first-in-class radiofluorinated inhibitor of PSMA.

Figure 2

Box plot of SUV_max for ¹⁸F-DCFBC PET–positive metastatic lesions by location and patient's androgen-resistant status (A) and box plot of average SUV for various regions of background physiologic uptake (B).

Figure 3

Anterior projection planar BS (A), ¹⁸F-DCFBC PET maximum-intensity projection (B), axial CT (C), and axial ¹⁸F-DCFBC PET/CT fusion (D) images from patient thought to have degenerative arthritic changes at site of ^99mTc-MDP uptake on bone scan (black arrowhead in A). However, intense focal ¹⁸F-DCFBC uptake was also noted at this site that progressed on follow-up corresponding to rise in prostate-specific antigen (black and white arrowheads in B–D).

Figure 4

¹⁸F-DCFBC PET maximum-intensity projection (A), axial CECT (B), and axial fused ¹⁸F-DCFBC PET/CT (C) images from patient with a subtle lytic bone lesion on CT that corresponded to intense ¹⁸F-DCFBC uptake in right posterolateral T5 vertebral body and progressed on follow-up as patient's prostate-specific antigen level continued to rise (black and white arrowheads in A–C).

Figure 5

¹⁸F-DCFBC PET maximum-intensity projection (A), axial CECT (B), and axial fused ¹⁸F-DCFBC PET/CT (C) images demonstrating intense ¹⁸F-DCFBC uptake in multiple small pelvic lymph nodes that had been deemed too small to be definitively disease-involved on CECT (black and white arrowheads in A–C). Lymph nodes decreased in size on follow-up imaging and correlated with fall in patient's prostate-specific antigen level to undetectable.

Figure 6

Posterior projection planar BS (A), ¹⁸F-DCFBC PET maximum-intensity projection (posterior view, B), axial CT (C), axial ¹⁸F-DCFBC PET (D), and axial fused ¹⁸F-DCFBC PET/CT (E) images from patient who was postprostatectomy with rising prostate-specific antigen and was naïve to systemic androgen-deprivation therapy and chemotherapy. Imaging demonstrates intense ^99mTc-MDP uptake on BS and corresponding dense sclerosis on CT of right scapula without significant ¹⁸F-DCFBC uptake (black and white arrowheads in A–E). This lesion progressed in extent to involve more of scapula on follow-up imaging in correlation with rising prostate-specific antigen level in this patient.