PSMA-Based [18F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer

Abstract

Purpose Current standard of care conventional imaging modalities (CIM) such as X-ray computed tomography (CT) and bone scan can be limited for detection of metastatic prostate cancer and therefore improved imaging methods are an unmet clinical need. We evaluated the utility of a novel second-generation low molecular weight radiofluorinated prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer, [18F]DCFPyL, in patients with metastatic prostate cancer. Procedures Nine patients with suspected prostate cancer recurrence, eight with CIM evidence of metastatic prostate cancer and one with biochemical recurrence, were imaged with [18F]DCFPyL PET/CT. Eight of the patients had contemporaneous CIM for comparison. A lesion-by-lesion comparison of the detection of suspected sites of metastatic prostate cancer was carried out between PET and CIM. Statistical analysis for estimated proportions of inter-modality agreement for detection of metastatic disease was calculated accounting for intra-patient correlation using general estimating equation (GEE) intercept-only regression models. Results One hundred thirty-nine sites of PET positive [18F]DCFPyL uptake (138 definite, 1 equivocal) for metastatic disease were detected in the eight patients with available comparison CIM. By contrast, only 45 lesions were identified on CIM (30 definite, 15 equivocal). When lesions were negative or equivocal on CIM, it was estimated that a large portion of these lesions or 0.72 (95 % confidence interval (CI) 0.55–0.84) would be positive on [18F]DCFPyL PET. Conversely, of those lesions negative or equivocal on [18F]DCFPyL PET, it was estimated that only a very small proportion or 0.03 (95 % CI 0.01–0.07) would be positive on CIM. Delayed 2-h-post-injection time point PET yielded higher tumor radiotracer uptake and higher tumor-to-background ratios than an earlier 1-h-post-injection time point. Conclusions A novel PSMA-targeted PET radiotracer, [18F]DCFPyL, was able to a large number of suspected sites of prostate cancer, many of which were occult or equivocal by CIM. This study provides strong preliminary evidence for the use of this second-generation PSMA-targeted PET radiotracer for detection of metastatic prostate cancer and lends further support for the importance of PSMA-targeted PET imaging in prostate cancer.

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).…”

“…However, delayed imaging might be considered in cases of equivocal findings or in the context of low PSA levels. Imaging with 18 F-labeled agents has been described at 60 min after injection and 120 min after injection, with preliminary evidence indicating an improvement in lesion detection with later-time-point imaging (32,82).…”

Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy

“…Subsequent analyses demonstrated markedly increased lesion detection efficiency relative to that of conventional imaging (84). In a head-to-head comparison of 14 selected patients who underwent 18 F-DCFPyL PET/CT after 68 Ga-PSMA-11 PET/CT because of negative or inconclusive findings, 18 F-DCFPyL PET/CT revealed additional lesions in 3 of 14 patients (21.4%) (85).…”

68Ga or18F for Prostate Cancer Imaging?

“…18 F-PSMA-1007 was reported favorable for primary tumors and local relapse because of low clearance via the urinary tract (1.2 percentage injected dose over 2 h). In contrast, urinary excretion of 18 F-DCFPyL, 68 Ga-PSMA-11, and 68 Ga-PSMA-617 is remarkably higher (.10 percentage injected dose over 2 h) (1,16,19). However, this improvement is related less to the radiolabeling moiety than to the optimized structure of the overall molecule.…”