Design, Synthesis, and Preclinical Evaluation of a Novel [¹⁸F]AlF-Labeling Positron Emission Tomography Tracer Targeting Prostate-Specific Membrane Antigen

Prostate-specific membrane antigen (PSMA) is a promising target for the detection and treatment of prostate cancer (PCa). However, current PSMA-targeting probes still exhibit suboptimal tumor uptake and retention, which limits their performance in positron emission tomography (PET) imaging of PCa. In this study, we developed a series of novel PSMA-targeting probes, among which NOTA-SP2A-PSMAL was selected. We then radiolabeled NOTA-SP2A-PSMAL with 18F and evaluated the in vitro and in vivo characteristics of [18F]AlF-SP2A-PSMAL. Subsequently, micro-PET/CT imaging and biodistribution studies were conducted in 22Rv1 and PC3 tumor-bearing mice to compare the in vivo distribution, tumor uptake, and retention of [18F]AlF-SP2A-PSMAL with [18F]AlF-PSMA-BCH. [18F]AlF-SP2A-PSMAL demonstrated favorable in vivo and in vitro properties. Micro-PET/CT imaging and biodistribution studies demonstrated that [18F]AlF-SP2A-PSMAL had satisfying pharmacokinetic characteristics and excellent targeting specificity for PSMA. Compared with [18F]AlF-PSMA-BCH, [18F]AlF-SP2A-PSMAL showed higher tumor uptake and better tumor retention. These results indicate that [18F]AlF-SP2A-PSMAL is a promising PET/CT tracer for diagnosing PCa.