¹⁸F-DCFBC PET/CT for PSMA-Based Detection and Characterization of Primary Prostate Cancer

Abstract

We previously demonstrated the ability to detect metastatic prostate cancer using N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC), a low-molecular-weight radiotracer that targets the prostate-specific membrane antigen (PSMA). PSMA has been shown to be associated with higher Gleason grade and more aggressive disease. An imaging biomarker able to detect clinically significant high-grade primary prostate cancer reliably would address an unmet clinical need by allowing for risk-adapted patient management.

Methods: We enrolled 13 patients with primary prostate cancer who were imaged with (18)F-DCFBC PET before scheduled prostatectomy, with 12 of these patients also undergoing pelvic prostate MR imaging. Prostate (18)F-DCFBC PET was correlated with MR imaging and histologic and immunohistochemical analysis on a prostate-segment (12 regions) and dominant-lesion basis. There were no incidental extraprostatic findings on PET suggestive of metastatic disease.

Results: MR imaging was more sensitive than (18)F-DCFBC PET for detection of primary prostate cancer on a per-segment (sensitivities of up to 0.17 and 0.39 for PET and MR imaging, respectively) and per-dominant-lesion analysis (sensitivities of 0.46 and 0.92 for PET and MR imaging, respectively). However, (18)F-DCFBC PET was more specific than MR imaging by per-segment analysis (specificities of 0.96 and 0.89 for PET and MR imaging for corresponding sensitivity, respectively) and specific for detection of high-grade lesions (Gleason 8 and 9) greater than 1.0 mL in size (4/4 of these patients positive by PET). (18)F-DCFBC uptake in tumors was positively correlated with Gleason score (ρ = 0.64; PSMA expression, ρ = 0.47; and prostate-specific antigen, ρ = 0.52). There was significantly lower (18)F-DCFBC uptake in benign prostatic hypertrophy than primary tumors (median maximum standardized uptake value, 2.2 vs. 3.5; P = 0.004).

Conclusion: Although the sensitivity of (18)F-DCFBC for primary prostate cancer was less than MR imaging, (18)F-DCFBC PET was able to detect the more clinically significant high-grade and larger-volume tumors (Gleason score 8 and 9) with higher specificity than MR imaging. In particular, there was relatively low (18)F-DCFBC PET uptake in benign prostatic hypertrophy lesions, compared with cancer in the prostate, which may allow for more specific detection of primary prostate cancer by (18)F-DCFBC PET. This study demonstrates the utility of PSMA-based PET, which may be used in conjunction with MR imaging to identify clinically significant prostate cancer.

Trial registration: ClinicalTrials.gov NCT01496157.

Keywords: MRI; PET/CT; primary prostate cancer; prostate specific membrane antigen (PSMA); prostatectomy.

FIGURE 1

¹⁸F-DCFBC chemical structure.

FIGURE 2

Correlation between focal uptake in right lateral prostate apex (arrowhead) on ¹⁸F-DCFBC PET (A), abnormal low T2 signal (arrowhead) on MR imaging (B), and tumor on gross surgical pathology, as outlined in green (C). Pathologic specimen from same tumor shows strong immunohistochemical staining for PSMA (brown color) (D).

FIGURE 3

Scatterplot of ¹⁸F-DCFBC PET SUV_max and prostatectomy Gleason score for pelvic 2D, pelvic 3D, and WB PET acquisitions showing strong positive correlation.

FIGURE 4

¹⁸F-DCFBC PET (A) and T2-weighted MR (B) images demonstrating ¹⁸F-DCFBC photopenia for representative example of BPH nodules (arrowheads) within central prostate.

FIGURE 5

Plot showing ranges of SUV_max in BPH, all PET-positive prostate cancers (nonstringent analysis), and tumors with PET positivity only in stringent analysis.