[18F]AlF-H3RESCA-PSMA

Prostate-specific membrane antigen (PSMA) has emerged as a pivotal biomarker for the molecular imaging and targeted therapy of prostate cancer. To address the ongoing need for PSMA-targeting radiotracers with improved mild-labeling capability and reduced non-target organ exposure, beyond currently approved agents (e.g., [⁶⁸Ga]Ga-PSMA-11) that require higher temperatures or show hepatobiliary clearance, a novel ¹⁸F-labeled PSMA inhibitor, [¹⁸F]AlF-H₃RESCA-PSMA, was developed for PET imaging of prostate cancer.

H₃RESCA-PSMA was synthesized with an acyclic pentadentate chelator and radiolabeled with [¹⁸F]AlF at room temperature. Biodistribution and PET/CT studies were performed in PSMA-positive tumor xenografts, with [¹⁸F]AlF-PSMA-RESCA1 as comparator.

Radiochemical yield was 75.5 ± 5.0%. [¹⁸F]AlF-H₃RESCA-PSMA showed 2-fold higher tumor uptake and slower wash-out versus PSMA-RESCA1, while exhibiting markedly reduced liver and kidney retention. PET images revealed superior tumor contrast and faster background clearance.

[¹⁸F]AlF-H₃RESCA-PSMA offers enhanced PSMA-targeting specificity and imaging contrast, supporting its clinical translation for prostate cancer PET.