PSA-Stratified Performance of F- and Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer.

Several studies outlined the sensitivity of 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 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 F-labeled PSMA tracer F-DCFPyL and the Ga-labeled reference Ga-PSMA-HBED-CC. We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using F-DCFPyL ( = 62, 269.8 MBq, PET scan at 120 min after injection) or Ga-PSMA-HBED-CC ( = 129, 158.9 MBq, 60 min after injection). 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 ( = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels ( = 4.3 × 10). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L ( = 2.4 × 10). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage ( = 3.4 × 10). For a PSA of 0.5-3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for F-DCFPyL and 66% (23/35) for Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA < 0.5 μg/L) or high (PSA > 3.5 μg/L). After radiotherapy ( = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of F-DCFPyL and Ga-PSMA-HBED-CC were strongly comparable ( = 2.71 × 10). However, in 36% of the PSMA-positive patients we detected additional lesions on the F-DCFPyL scan ( = 3.7 × 10). Our data suggest that F-DCFPyL is noninferior to Ga-PSMA-HBED-CC, while offering the advantages of F labeling. Our results indicate that imaging with 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 F-DCFPyL and 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 F-DCFPyL in future prospective trials.