PSA-Stratified Performance of ¹⁸F- and ⁶⁸Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer

Abstract

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 withF 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 tracerF-DCFPyL and the Ga-labeled referenceGa-PSMA-HBED-CC. We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols usingF-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) forGa-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 andGa-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 thatF-DCFPyL is noninferior to Ga-PSMA-HBED-CC, while offering the advantages ofF 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 forF-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 ofF-DCFPyL in future prospective trials.

PSMA Ligands for PET Imaging of Prostate Cancer

“…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). A follow-up study from the same group using PSA-adjusted parallel biochemically recurrent PC patient cohorts (including a total of 191 patients) found that 18 F-DCFPyL was noninferior to 68 Ga-PSMA-11 (45) and suggested an improved sensitivity of the 18 F-labeled radiotracer in the PSA range of 0.5-3.5 ng/mL (with the caveat that different injected doses and acquisition parameters were used for the 2 PSMA-targeted agents). Further indepth clinical studies with standardized acquisition protocols and histologic validation are needed to establish the comparative performance of these 2 radiotracers.…”

Prostate Specific Membrane Antigen Targeted 18 F-DCFPyL Positron Emission Tomography/Computerized Tomography for the Preoperative Staging of High Risk Prostate Cancer: Results of a Prospective, Phase II, Single Center Study

“…17,18 Furthest along in clinical development is the 18 F-DCFPyL radiotracer, which was first described by Chen et al 19 This radiotracer has been examined in several studies in the context of imaging biochemically recurrent or metastatic PCa. 20–22 …”

Initial evaluation of PET/CT with 18F‐FSU‐880 targeting prostate‐specific membrane antigen in prostate cancer patients

“…In the remaining patient (case 5), known bone metastases showed very low uptake of 18 F‐FSU‐880 with a TBR < 1 at all time points. It is reported for 68 Ga‐ and 18 F‐labeled PSMA probes that, in biochemical recurrence, patients with low serum PSA levels showed a low detection rate . When PET/CT was carried out at very early stage with low PSA level, the lesion size was too small to be detected due to partial‐volume effect.…”