Abstract
Introduction: 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. Methods: The non-radioactive reference compound PSMA-1007 and the labeling precursor were built up by solid phase chemistry. The radioligand 18F-PSMA-1007 was produced via a two-step procedure using the prosthetic group 6-18F-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester (6-18F-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. Results: 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. Conclusion: 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 18F-PSMA-1007 for clinical transfer as diagnostic PET tracer for prestaging and monitoring of prostate cancer.
- Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.