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

OBJECTIVE - 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).

CONCLUSIONS - 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.

J Nucl Med. 2015 Jul;56(7):1003-10. doi: 10.2967/jnumed.115.154336. Epub 2015 Jun 11.

Rowe SP1, Gage KL1, Faraj SF2, Macura KJ3, Cornish TC2, Gonzalez-Roibon N2, Guner G2, Munari E2, Partin AW4, Pavlovich CP4, Han M4, Carter HB4, Bivalacqua TJ4, Blackford A1, Holt D1, Dannals RF1, Netto GJ5, Lodge MA1, Mease RC1, Pomper MG1, Cho SY6.

1 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
2 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
3 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland; and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
4 The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland; and.
5 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland; and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
6 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland