H3RESCA chelator-enabled [18F]AlF labeling: An optimized temperature-resilient platform for PSMA-targeted PET tracers in prostate cancer.

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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