Preclinical and clinical evaluation of [64Cu]Cu-PSMA-Q PET/CT for prostate cancer detection and its comparison with [18F]FDG imaging

This study aimed to develop and evaluate [⁶⁴Cu]Cu-PSMA-Q as a novel positron emission tomography (PET) imaging agent for prostate cancer detection, assessing its diagnostic accuracy and clinical applicability in comparison to [¹⁸F]FDG PET imaging. [⁶⁴Cu]Cu-PSMA-Q was synthesized, purified, and subjected to comprehensive quality control. Its binding affinity, cellular uptake, and internalization were assessed in vitro using prostate-specific membrane antigen (PSMA)-positive LNCaP C4-2B cells. In vivo toxicity studies were conducted in 12 mouse models (6 per group). Small-animal PET/CT (positron emission tomography/computed tomography) imaging and biodistribution studies were performed on tumor-bearing mice. Clinical evaluation involved PET/CT imaging with [⁶⁴Cu]Cu-PSMA-Q in 29 prostate cancer patients, with comparative analysis against [¹⁸F]FDG PET/CT imaging. Radiation dosimetry was calculated using OLINDA/EXM software, and diagnostic performance metrics, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and tumor-to-background ratio, were analyzed using SPSS v24.0, with P < 0.05 considered statistically significant. Comparative analyses utilized t-tests or Mann-Whitney U tests as appropriate. [⁶⁴Cu]Cu-PSMA-Q achieved over 99% radiochemical purity and a specific activity of 20.5 ± 1 GBq/μmol. In vitro studies demonstrated a dissociation constant (Kd) of 4.083 nM, along with high cellular uptake and internalization in LNCaP C4-2B cells. No significant toxicity was observed in mouse models. Small -animal PET/CT imaging revealed peak tumor uptake at 4 h post-injection in LNCaP C4-2B tumor xenografts. In clinical evaluations, [⁶⁴Cu]Cu-PSMA-Q PET/CT detected more lesions than [¹⁸F]FDG, with significantly higher SUVmax, SUVmean, and tumor-to-background ratios. The mean effective radiation dose was calculated as 4.48 ± 0.99 mSv. [⁶⁴Cu]Cu-PSMA-Q PET/CT demonstrated superior lesion detection and higher tumor-to-background ratios compared to [¹⁸F]FDG PET/CT for prostate cancer visualization. Its advantageous properties, including a favorable half-life, excellent safety profile, and enhanced diagnostic accuracy, support its potential for broad clinical adoption. This study establishes a foundation for further validation of [⁶⁴Cu]Cu-PSMA-Q in prostate cancer management.