Efficient radiosynthesis of a new PSMA ligand: [Al18F]DTPA-CHX-DUPA-Pep

Objectives The targeting of prostate specific membrane antigen (PSMA) has become highly attractive for molecular imaging of prostate cancer with PET/CT in the last years. Particularly, clinical application of [68Ga]-labeled PSMA ligands, bearing urea moieties such as DUPA, are of great interest. Instead of a Ge-68/Ga-68 generator, for centers having a cyclotron for [18F]fluoride production, radiofluorination via Al18F2+ appears to be a good alternative. Therefore, DUPA-Pep was coupled to DTPA-CHX-A” which shows higher thermodynamic as well as good in-vivo stability in comparison to NOTA as verified in additional experiments.

Methods Na18F was eluted by 0.9%NaCl after fixing of [18F]fluoride on a Waters Sep Pak QMA-light cartridge and added to each vial containing 20µL of peptide (1, 10, 25, 50, 100, or 200µg in 0.05M NaOAc, pH: 5.5) and 3µL of 0.01M AlCl3.6H2O solution in 0.05M NaOAc. Experiments were carried out between 60-100°C for 1, 5, 10, 20, and 30min. Analyses were performed by radio-TLC (75%MeCN, Rf: 0.78).Additionally, the product fractions after gradient elution by radio-HPLC (C18, 250x4.6mm, A:MeCN/0.1%TFA, B:water/0.1%TFA, 2mL/min; Rt: 9.7min, Rt Al18F2+: 1.6min) were collected for γ-counter analyses, too. For final formulation, [Al18F]DTPA-CHX-A”-DUPA-Pep was eluted after solid phase extraction from Waters Sep Pak C18-light cartridge with 1mL of EtOH.

Results With 200µg to 100µg at 100°C, maximum RCYs (≥90%) were obtained at 5min with decrease to 79% at 30min. Using 50µg at 100°C , RCY of 89±1% was obtained at 5min and 87±1.4% after 1min at 60°C. However, with 1µg at 60°C, RCY was 13±1% (30min, radio-HPLC). The stability studies in serum at 37°C showed no free Al18F2+ after 6h. The quality control showed ≥98% radiochemical purity.

Conclusions [Al18F]DTPA-CHX-A”-DUPA-Pep was efficiently and fast prepared by using Al18F2+ in RCYs of 90% providing complete serum stability with the advantage of the longer half-life compared to the [68Ga]-labeled compound.