Radiofluorination of PSMA-HBED via Al18F2+ Chelation and Biological Evaluations In Vitro
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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 [Al18F]2+. In the present study, the radiofluorinations of a well-known PSMA ligand Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (PSMA-HBED) via [Al18F]2+ were performed with respect to various reaction parameters, along with the biological evaluations in a cell experiment.
[Al18F]PSMA-HBED was prepared by adding Na[18F]F into a vial containing 0.026 μmol peptide (in 0.05 M NaOAc buffer) and 0.03 μmol AlCl3⋅6H2O (in 0.05 M NaOAc buffer). Then, it was stirred at different temperatures from 1 to 30 min. 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 0.026 μmol peptide (30 °C, 5 min). For preclinical experiments, the production of [Al18F]PSMA-HBED at 35 °C including purification by solid phase extraction (SPE) succeeded within 45 min, 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 4 h as well as a promising binding coefficient (K D) value of 10.3 ± 2.2 nM in cell experiments with PSMA-positive LNCaP C4-2 cells.
An efficient and one-pot method for the radiosynthesis of [Al18F]PSMA-HBED was developed (0.26 μmol of precursor at 35 °C). In cell culture studies, the K D suggests [Al18F]PSMA-HBED as a potential PSMA ligand for future investigations in vivo and clinical applications afterwards.
Key wordsF-18 Al18F-labeling PSMA PSMA-HBED Prostate cancer
Conflict of Interest
The authors declare that they have no conflict of interest.
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