title: PSA-Stratified Performance of18F- and68Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer.
abstract: Several studies outlined the sensitivity of68Ga-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 with18F 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 the18F-labeled PSMA tracer18F-DCFPyL and the68Ga-labeled reference68Ga-PSMA-HBED-CC.Methods:We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using18F-DCFPyL (n= 62, 269.8 MBq, PET scan at 120 min after injection) or68Ga-PSMA-HBED-CC (n= 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.Results:After prostatectomy (n= 106), the sensitivity of both tracers was significantly associated with absolute PSA levels (P= 4.3 × 10-3). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L (P= 2.4 × 10-5). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage (P= 3.4 × 10-6). For a PSA of 0.5-3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for18F-DCFPyL and 66% (23/35) for68Ga-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 (n= 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of18F-DCFPyL and68Ga-PSMA-HBED-CC were strongly comparable (P= 2.71 × 10-8). However, in 36% of the PSMA-positive patients we detected additional lesions on the18F-DCFPyL scan (P= 3.7 × 10-2).Conclusion:Our data suggest that18F-DCFPyL is noninferior to68Ga-PSMA-HBED-CC, while offering the advantages of18F labeling. Our results indicate that imaging with18F-DCFPyL may even exhibit improved sensitivity in localizing relapsed tumors after prostatectomy for moderately increased PSA levels. Although the standard acquisition protocols, used for18F-DCFPyL and68Ga-PSMA-HBED-CC in this study, stipulate different activity doses and tracer uptake times after injection, our findings provide a promising rationale for validation of18F-DCFPyL in future prospective trials.
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany felix.dietlein@uni-koeln.de.|Center of Integrated Oncology Cologne Bonn, University Hospital of Cologne, Cologne, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Dietlein
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.|Center of Integrated Oncology Cologne Bonn, University Hospital of Cologne, Cologne, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Kobe
authors.affiliation: West-German Prostate Center, Klinik am Ring, Cologne, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Neubauer
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.|Center of Integrated Oncology Cologne Bonn, University Hospital of Cologne, Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Stockter
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schomäcker
authors.affiliation: Department of Urology, University Hospital of Cologne, Cologne, Germany; and.
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
authors.affiliation: Institute of Radiochemistry and Experimental Molecular Imaging, University Hospital of Cologne, Cologne, Germany.
authors.forename: Boris D
authors.initials: BD
authors.lastname: Zlatopolskiy
authors.affiliation: Institute of Radiochemistry and Experimental Molecular Imaging, University Hospital of Cologne, Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.|Center of Integrated Oncology Cologne Bonn, University Hospital of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.|Center of Integrated Oncology Cologne Bonn, University Hospital of Cologne, Cologne, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Dietlein
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D004492:Edetic Acid / Q000031:analogs & derivatives; D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008239:Lysine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging* / Q000453:epidemiology* / Q000601:surgery; D009842:Oligopeptides; D009942:Organometallic Compounds; D015995:Prevalence; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000453:epidemiology* / Q000601:surgery; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014508:Urea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: C572626:2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid; D014408:Biomarkers, Tumor; D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D009842:Oligopeptides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C000718244:gallium 68 PSMA-11; D014508:Urea; D004492:Edetic Acid; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D008239:Lysine
keywords: 18F-DCFPyL; 68Ga-PSMA-HBED-CC; PSMA ligands; biochemical recurrence; prostate cancer