Radiofluorination of PSMA-HBED via Al(18)F(2+) Chelation and Biological Evaluations In Vitro.

Abstract

Ga-68-labeled prostate-specific membrane antigen (PSMA) ligands have been used clinically for positron emission tomography (PET) imaging of prostate cancer. However, F-18-labeled compounds offer several advantages, including the potential for delayed imaging, high starting activities enabling multidose preparation, and improved spatial resolution in PET. For F-18 labeling of peptides conjugated with a suitable chelator, a fast and feasible method is the use of [Al(18)F](2+). In the present study, the radiofluorinations of a well-known PSMA ligand Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (PSMA-HBED) via [Al(18)F](2+) were performed with respect to various reaction parameters, along with the biological evaluations in a cell experiment. [Al(18)F]PSMA-HBED was prepared by adding Na[(18)F]F into a vial containing 0.026μmol peptide (in 0.05M NaOAc buffer) and 0.03μmol AlCl3⋅6H2O (in 0.05M NaOAc buffer). Then, it was stirred at different temperatures from 1 to 30min. Afterwards, purification was carried out by solid phase extraction. Biological evaluations were performed in PSMA-positive cell lines LNCaP C4-2, along with a negative control using PC-3 cell lines. The best labeling results (81 ± 0.5%, n = 4) were observed with 0.026μmol peptide (30°C, 5min). For preclinical experiments, the production of [Al(18)F]PSMA-HBED at 35°C including purification by solid phase extraction (SPE) succeeded within 45min, resulting in a radiochemical yield of 49 ± 1.2% (decay-corrected, n = 6, radiochemical purity ≥98%) at EOS. The labeled peptide revealed serum stability for 4h as well as a promising binding coefficient (K D) value of 10.3 ± 2.2nM in cell experiments with PSMA-positive LNCaP C4-2 cells. An efficient and one-pot method for the radiosynthesis of [Al(18)F]PSMA-HBED was developed (0.26μmol of precursor at 35°C). In cell culture studies, the K D suggests [Al(18)F]PSMA-HBED as a potential PSMA ligand for future investigations in vivo and clinical applications afterwards.