• Jens Cardinale, Martin Schäfer, Martina Benešová, Ulrike Bauder-Wüst, Karin Leotta, Matthias Eder, Oliver C Neels, Uwe Haberkorn, Frederik L Giesel, and Klaus Kopka.
• Division of Radiopharmaceutical Chemistry, German Cancer Research Center, INF 280, Heidelberg, Germany; and j.cardinale@dkfz.de.
• J. Nucl. Med. 2017 Mar 1; 58 (3): 425-431.

AbstractIn 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 of 18F-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 radioligand 18F-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 radioligand 18F-PSMA-1007 for use as a diagnostic PET tracer in prestaging and monitoring of prostate cancer.© 2017 by the Society of Nuclear Medicine and Molecular Imaging.

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