title: Prospective Comparison of 18F-Fluoromethylcholine Versus 68Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy.
abstract: In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. (11)C-choline and (18)F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. (68)Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga-N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of (68)Ga-PSMA versus (18)F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy, radiation treatment, or both and were being considered for targeted therapy.
  
  
  METHODS
  A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. (68)Ga-PSMA, (18)F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible.
  
  
  RESULTS
  In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with (68)Ga-PSMA alone, 11 (42%) with both (18)F-fluoromethylcholine and (68)Ga-PSMA, and only 1 (4%) with (18)F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for (68)Ga-PSMA versus 12.5% for (18)F-fluoromethylcholine. When PSA was 0.5-2.0 ng/mL, the detection rate was 69% for (68)Ga-PSMA versus 31% for (18)F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for (68)Ga-PSMA versus 57% for (18)F-fluoromethylcholine. On lesion-based analysis, (68)Ga-PSMA detected more lesions than (18)F-fluoromethylcholine (59 vs. 29, P < 0.001). The tumor-to-background ratio in positive scans was higher for (68)Ga-PSMA than for (18)F-fluoromethylcholine (28.6 for (68)Ga-PSMA vs. 9.4 for (18)F-fluoromethylcholine, P < 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to (68)Ga-PSMA imaging alone. Histologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 (68)Ga-PSMA-positive lesions were consistent with prostate cancer ((68)Ga-PSMA was true-positive). The lesion positive on (18)F-fluoromethylcholine imaging and negative on (68)Ga-PSMA imaging was shown at biopsy to be a false-positive (18)F-fluoromethylcholine finding ((68)Ga-PSMA was true-negative).
  
  
  CONCLUSIONS
  In patients with biochemical failure and a low PSA level, (68)Ga-PSMA demonstrated a significantly higher detection rate than (18)F-fluoromethylcholine and a high overall impact on management.
authors.affiliation: Department of Diagnostic Imaging, St. Vincent's Public Hospital, Sydney, Australia Nuclear Medicine Operative Unit, Policlinico S. Orsola-Malpighi Hospital, Bologna, Italy joshuajames.morigi@studio.unibo.it.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Morigi
authors.affiliation: St. Vincent's Prostate Cancer Centre, St. Vincent's Clinic, Sydney, Australia Australian Prostate Cancer Research Centre, Garvan Institute of Medical Research/Kinghorn Cancer Centre, Sydney, New South Wales, Australia.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Stricker
authors.affiliation: St. Vincent's Prostate Cancer Centre, St. Vincent's Clinic, Sydney, Australia Australian Prostate Cancer Research Centre, Garvan Institute of Medical Research/Kinghorn Cancer Centre, Sydney, New South Wales, Australia.
authors.forename: Pim J
authors.initials: PJ
authors.lastname: van Leeuwen
authors.affiliation: Department of Diagnostic Imaging, St. Vincent's Public Hospital, Sydney, Australia University of New South Wales, Sydney, New South Wales, Australia; and.
authors.forename: Reuben
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Diagnostic Imaging, St. Vincent's Public Hospital, Sydney, Australia.
authors.forename: Bao
authors.initials: B
authors.lastname: Ho
authors.affiliation: St. Vincent's Prostate Cancer Centre, St. Vincent's Clinic, Sydney, Australia Australian Prostate Cancer Research Centre, Garvan Institute of Medical Research/Kinghorn Cancer Centre, Sydney, New South Wales, Australia.
authors.forename: Quoc
authors.initials: Q
authors.lastname: Nguyen
authors.affiliation: University of Sydney, Sydney, New South Wales, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Hruby
authors.affiliation: St. Vincent's Prostate Cancer Centre, St. Vincent's Clinic, Sydney, Australia.
authors.forename: Gerald
authors.initials: G
authors.lastname: Fogarty
authors.affiliation: St. Vincent's Prostate Cancer Centre, St. Vincent's Clinic, Sydney, Australia.
authors.forename: Raj
authors.initials: R
authors.lastname: Jagavkar
authors.affiliation: University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kneebone
authors.affiliation: Department of Diagnostic Imaging, St. Vincent's Public Hospital, Sydney, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Hickey
authors.affiliation: Nuclear Medicine Operative Unit, Policlinico S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fanti
authors.affiliation: Department of Diagnostic Imaging, St. Vincent's Public Hospital, Sydney, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Tarlinton
authors.affiliation: Department of Diagnostic Imaging, St. Vincent's Public Hospital, Sydney, Australia University of New South Wales, Sydney, New South Wales, Australia; and.
authors.forename: Louise
authors.initials: L
authors.lastname: Emmett
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000737:chemistry*; D001706:Biopsy; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005189:False Positive Reactions; D005710:Gallium Radioisotopes / Q000008:administration & dosage*; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D016879:Salvage Therapy / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000954:Antigens, Surface; D005710:Gallium Radioisotopes; C516370:fluoromethylcholine; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen; D002794:Choline
keywords: 18F-fluoromethylcholine; 68Ga-PSMA; PET/CT; molecular imaging; prostate cancer; prostate-specific membrane antigen