Chen Fei, Zhang Hao, Zhan Yousheng, Huang Xiaohong, He Zongxi, Ma Daiyuan, Tang Tielong, Li Suping
Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
Sichuan Key Laboratory of Medical Imaging, North Sichuan Medical College, Nanchong, Sichuan, China.
Sci Rep. 2025 Apr 25;15(1):14431. doi: 10.1038/s41598-025-98757-8.
This study aimed to develop and evaluate [Cu]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 [F]FDG PET imaging. [Cu]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 [Cu]Cu-PSMA-Q in 29 prostate cancer patients, with comparative analysis against [F]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. [Cu]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, [Cu]Cu-PSMA-Q PET/CT detected more lesions than [F]FDG, with significantly higher SUVmax, SUVmean, and tumor-to-background ratios. The mean effective radiation dose was calculated as 4.48 ± 0.99 mSv. [Cu]Cu-PSMA-Q PET/CT demonstrated superior lesion detection and higher tumor-to-background ratios compared to [F]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 [Cu]Cu-PSMA-Q in prostate cancer management.
本研究旨在开发并评估[铜]Cu-PSMA-Q作为一种用于前列腺癌检测的新型正电子发射断层扫描（PET）成像剂，与[氟]FDG PET成像相比，评估其诊断准确性和临床适用性。合成、纯化了[铜]Cu-PSMA-Q，并进行了全面的质量控制。使用前列腺特异性膜抗原（PSMA）阳性的LNCaP C4-2B细胞在体外评估其结合亲和力、细胞摄取和内化情况。在12只小鼠模型（每组6只）中进行了体内毒性研究。对荷瘤小鼠进行了小动物PET/CT（正电子发射断层扫描/计算机断层扫描）成像和生物分布研究。临床评估包括对29例前列腺癌患者进行[铜]Cu-PSMA-Q的PET/CT成像，并与[氟]FDG PET/CT成像进行对比分析。使用OLINDA/EXM软件计算辐射剂量学，并使用SPSS v24.0分析诊断性能指标，包括最大标准化摄取值（SUVmax）、平均标准化摄取值（SUVmean）和肿瘤与背景比值，P < 0.05被认为具有统计学意义。根据情况，比较分析采用t检验或曼-惠特尼U检验。[铜]Cu-PSMA-Q的放射化学纯度超过99%，比活度为20.5 ± 1 GBq/μmol。体外研究表明其解离常数（Kd）为4.083 nM，在LNCaP C4-2B细胞中具有高细胞摄取和内化。在小鼠模型中未观察到明显毒性。小动物PET/CT成像显示，在LNCaP C4-2B肿瘤异种移植模型中，注射后4小时肿瘤摄取达到峰值。在临床评估中，[铜]Cu-PSMA-Q PET/CT检测到的病变比[氟]FDG更多，SUVmax、SUVmean和肿瘤与背景比值显著更高。平均有效辐射剂量计算为4.48 ± 0.99 mSv。与[氟]FDG PET/CT相比，[铜]Cu-PSMA-Q PET/CT在前列腺癌可视化方面显示出更好的病变检测能力和更高的肿瘤与背景比值。其有利的半衰期、良好地安全性和更高的诊断准确性等优势特性，支持其在临床上广泛应用的潜力。本研究为进一步验证[铜]Cu-PSMA-Q在前列腺癌管理中的应用奠定了基础。
