PSA-stratified performance of 18F- and 68Ga-labeled tracers in PSMA-PET imaging of patients with biochemical recurrence of prostate cancer.

Several studies outlined the sensitivity of (68)Ga-labeled PET tracers against the prostate-specific membrane antigen (PSMA) for localization of relapsed prostate cancer in patients with renewed increase in the prostate-specific antigen (PSA), commonly referred to as biochemical recurrence. Labeling of PSMA tracers with (18)F offers numerous advantages, including improved image resolution, longer half-life and increased production yields. The aim of this study was to assess the PSA-stratified performance of the (18)F-labeled PSMA tracer (18)F-DCFPyL and the (68)Ga-labeled reference (68)Ga-PSMA-HBED-CC.

We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols with (18)F-DCFPyL (N = 62, 269.8 MBq, PET scan at 120 minutes p.i.) or (68)Ga-PSMA-HBED-CC (N = 129, 158.9 MBq, 60 minutes p.i.). We determined PSA-stratified sensitivity rates for both tracers and corrected our calculations for Gleason scores using iterative matched-pair analyses. As an orthogonal validation, we directly compared tracer distribution patterns in a separate cohort of 25 patients, sequentially examined with both tracers.

After prostatectomy (N = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels (P = 4.3x10-3). Sensitivity increased abruptly, when PSA values exceeded 0.5µg/L (P = 2.4x10-5). For PSA <3.5µg/L, most relapses were diagnosed at a still limited stage (P = 3.4x10-6). For PSA of 0.5-3.5µg/L, PSA-stratified sensitivity was 88% (15/17) for (18)F-DCFPyL and 66% (23/35) for (68)Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA <0.5µg/L) or high (PSA >3.5µg/L). After radiotherapy (N = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of (18)F-DCFPyL and (68)Ga-PSMA-HBED-CC were strongly comparable (P = 2.71x10-8). However, in 36% of the PSMA-positive patients we detected additional lesions on the (18)F-DCFPyL scan (P = 3.7x10-2).

Our data suggest that (18)F-DCFPyL is non-inferior to (68)Ga-PSMA-HBED-CC, while offering the advantages of (18)F-labeling. Our results indicate that imaging with (18)F-DCFPyL may even exhibit improved sensitivity in localizing relapsed tumors after prostatectomy for moderately increased PSA levels. Although the standard acquisition protocols, used for (18)F-DCFPyL and (68)Ga-PSMA-HBED-CC in this study, stipulate different activity doses and tracer uptake times after injection, our findings provide a promising rationale for validation of (18)F-DCFPyL in future prospective trials.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016 Jan 01 [Epub ahead of print]

Felix Dietlein, Carsten Kobe, Stephan Neubauer, Matthias Schmidt, Simone Stockter, Thomas Fischer, Klaus Schomäcker, Axel Heidenreich, Boris D Zlatopolskiy, Bernd Neumaier, Alexander Drzezga, Markus Dietlein

University Hospital of Cologne, Germany., West-German Prostate Center, Germany., University of Cologne, Germany.