Preclinical evaluation and dosimetry of [64Cu/67Cu]Cu-NGUL for PSMA-targeted prostate cancer theranostics.

BACKGROUND

Prostate-specific membrane antigen (PSMA) is a promising target for imaging and theranostics in prostate cancer (PCa). Current PSMA tracers face limitations due to short half-lives and logistics. We developed a PSMA-targeted PET radiotracer, [64Cu]Cu-NGUL and [67Cu]Cu-NGUL, and evaluated their preclinical feasibility.

METHODS

Radiolabeling parameters (ligand concentration, pH, temperature, incubation time) were optimized and stability was assessed in buffer and human serum at 37 °C for 60 h. In vitro uptake was measured in PSMA-positive (22Rv1) and PSMA-negative (PC-3) cells. Biodistribution, PET imaging, and dosimetry-based effective dose estimation were performed in 22Rv1 xenograft models.

RESULTS

[64Cu]Cu-NGUL was obtained with >99 % yield (n = 3) and excellent stability for 60 h. Uptake in 22Rv1 cells was approximately fivefold higher than in PC-3 (n = 3, p < 0.001). Biodistribution showed rapid renal clearance with tumor uptake of 16.3 %ID/g at 0.17 h, decreasing over 24 h (n = 4). PET confirmed clear, PSMA-specific tumor localization at all imaging time points (SUV 0.28 ± 0.04 at 2 h). The estimated effective dose was 0.01 mSv/MBq.

CONCLUSION

[64Cu]Cu-NGUL was efficiently radiolabeled and demonstrated PSMA-specific uptake in vitro and in vivo, supporting its potential for clinical translation as a PSMA-targeted tracer. Dosimetry findings indicate a favorable safety profile and warrant further evaluation of its 67Cu analogue for theranostic applications in PCa.