Preclinical Evaluation of [18F]PSMA-1007: A New PSMA-Ligand for Prostate Cancer Imaging.

In recent years several radiotracers targeting the prostate-specific membrane antigen (PSMA) have been introduced. Few of those had a high clinical impact for the treatment of patients suffering from prostate cancer. However, the number of fluorine-18 labeled tracers addressing PSMA is still limited. Therefore, we aimed at the development of a radiofluorinated molecule with emphasis on resembling the structure of the therapeutic PSMA-617.

The non-radioactive reference compound PSMA-1007 and the labeling precursor were built up by solid phase chemistry. The radioligand (18)F-PSMA-1007 was produced via a two-step procedure using the prosthetic group 6-(18)F-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester (6-(18)F-F-Py-TFP). The binding affinity of the ligand towards PSMA and its internalization properties were evaluated in vitro using PSMA-positive LNCaP (Lymph Node Carcinoma of the Prostate) cells. Further, organ distribution studies were performed using LNCaP- and PC-3 (Prostate Cancer cell line; PSMA negative) tumor bearing mice. Finally, a microPET (small animal Positron Emission Tomography) imaging with an LNCaP tumor bearing mouse was carried out.

The identified ligand revealed a binding affinity of 6.7±1.7 nM towards PSMA and an exceptional high internalization ratio of 67±13 % in vitro. In organ distribution studies a high and specific tumor uptake of 8.0±2.4 %ID/g in LNCaP tumor bearing mice was observed. In further microPET experiments LNCaP tumors were clearly visualized.

The radiofluorinated PSMA-ligand showed promising characteristics in its preclinical evaluation and the feasibility of prostate cancer imaging was demonstrated by microPET studies. Thus, we recommend the ligand (18)F-PSMA-1007 for clinical transfer as diagnostic PET tracer for prestaging and monitoring of prostate cancer.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016 Oct 27 [Epub ahead of print]

Jens Cardinale, Martin Schäfer, Martina Benešová, Ulrike Bauder-Wüst, Karin Leotta, Matthias Eder, Oliver C Neels, Uwe Haberkorn, Frederik L Giesel, Klaus Kopka

German Cancer Research Center, Germany., German Cancer Research Center (DKFZ)., University Hospital Heidelberg.