Synthesis and preclinical evaluation of an Al¹⁸F radiofluorinated bivalent PSMA ligand

Prostate-specific membrane antigen (PSMA) has become as an outstanding prostate cancer-related target for diagnostic imaging and targeted radiotherapy. Clinical studies on a few PSMA radiotracers are currently underway to determine their efficacy as imaging agents to detect prostate cancer. To improve tumor retention and tumor-to-normal tissue contrast, we herein report the synthesis and preclinical evaluation of an Al¹⁸F-labeled bivalent PSMA ligand (¹⁸F-Bi-PSMA). ¹⁸F-Bi-PSMA was successful automated preparation and in vitro evaluation showed that ¹⁸F-Bi-PSMA was potent binding affinity, high specificity, and rapid internalization in PSMA-expressing cells. Biodistribution studies revealed a high and specific tumor uptake of 20.5 ± 3.5 %ID/g in 22Rv1 tumor-bearing mice. Furthermore, compared to the clinically used monomeric PSMA-targeting tracers, ⁶⁸Ga-PSMA-11 and ¹⁸F-PSMA-1007, ¹⁸F-Bi-PSMA exhibited improved pharmacokinetics and higher tumor uptake, as well as better tumor-to-normal tissue contrast, resulting in considerably high imaging quality. Our findings indicated that the bivalent PSMA radioligand, ¹⁸F-Bi-PSMA, was successfully synthesized and ideal imaging properties.