title: Preclinical Evaluation of18F-PSMA-1007, a New Prostate-Specific Membrane Antigen Ligand for Prostate Cancer Imaging.
abstract: In recent years, several radiotracers targeting the prostate-specific membrane antigen (PSMA) have been introduced. Some of them have had a high clinical impact on the treatment of patients with prostate cancer. However, the number of18F-labeled tracers addressing PSMA is still limited. Therefore, we aimed to develop a radiofluorinated molecule resembling the structure of therapeutic PSMA-617.Methods:The nonradioactive reference compound PSMA-1007 and the precursor were produced by solid-phase chemistry. The radioligand18F-PSMA-1007 was produced by a 2-step procedure with the prosthetic group 6-18F-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester. The binding affinity of the ligand for PSMA and its internalization properties were evaluated in vitro with PSMA-positive LNCaP (lymph node carcinoma of the prostate) cells. Further, organ distribution studies were performed with mice bearing LNCaP and PC-3 (prostate cancer cell line; PSMA-negative) tumors. Finally, small-animal PET imaging of an LNCaP tumor-bearing mouse was performed.Results:The identified ligand had a binding affinity of 6.7 ± 1.7 nM for PSMA and an exceptionally high internalization ratio (67% ± 13%) in vitro. In organ distribution studies, high and specific tumor uptake (8.0 ± 2.4 percentage injected dose per gram) in LNCaP tumor-bearing mice was observed. In the small-animal PET experiments, LNCaP tumors were clearly visualized.Conclusion:The radiofluorinated PSMA ligand showed promising characteristics in its preclinical evaluation, and the feasibility of prostate cancer imaging was demonstrated by small-animal PET studies. Therefore, we recommend clinical transfer of the radioligand18F-PSMA-1007 for use as a diagnostic PET tracer in prestaging and monitoring of prostate cancer.
authors: Division of Radiopharmaceutical Chemistry, German Cancer Research Center, INF 280, Heidelberg, Germany; and j.cardinale@dkfz.de.
authors: Jens
authors: J
authors: Cardinale
authors: Division of Radiopharmaceutical Chemistry, German Cancer Research Center, INF 280, Heidelberg, Germany; and.
authors: Martin
authors: M
authors: Schäfer
authors: Division of Radiopharmaceutical Chemistry, German Cancer Research Center, INF 280, Heidelberg, Germany; and.
authors: Martina
authors: M
authors: Benešová
authors: Division of Radiopharmaceutical Chemistry, German Cancer Research Center, INF 280, Heidelberg, Germany; and.
authors: Ulrike
authors: U
authors: Bauder-Wüst
authors: Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, Heidelberg, Germany.
authors: Karin
authors: K
authors: Leotta
authors: Division of Radiopharmaceutical Chemistry, German Cancer Research Center, INF 280, Heidelberg, Germany; and.
authors: Matthias
authors: M
authors: Eder
authors: Division of Radiopharmaceutical Chemistry, German Cancer Research Center, INF 280, Heidelberg, Germany; and.
authors: Oliver C
authors: OC
authors: Neels
authors: Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, Heidelberg, Germany.
authors: Uwe
authors: U
authors: Haberkorn
authors: Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, Heidelberg, Germany.
authors: Frederik L
authors: FL
authors: Giesel
authors: Division of Radiopharmaceutical Chemistry, German Cancer Research Center, INF 280, Heidelberg, Germany; and.
authors: Klaus
authors: K
authors: Kopka
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods*; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000954:Antigens, Surface; D004151:Dipeptides; D005462:Fluorine Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; C000602389:PSMA-617; D019275:Radiopharmaceuticals; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen
keywords: 18F; PET; PSMA; prostate cancer