Jan Gowsia, Passi Neelima D, Dhawan Devinder Kumar, Chadha Vijayta Dani
1 Center for Nuclear Medicine (UIEAST), Panjab University , Chandigarh, India .
2 University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh, India .
Cancer Biother Radiopharm. 2017 Mar;32(2):39-47. doi: 10.1089/cbr.2016.2032. Epub 2017 Feb 22.
This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with Tc and showed >90% labeling efficiency. The radiopharmaceutical was found to be stable up to 6 hours in rat serum at 37°C. The blood kinetics of the Tc-finasteride followed a biphasic release pattern, whereby fast-release phase was observed at 15 seconds and a slow-release phase was observed after 30 minutes of administration. The plasma protein binding of the radio complex observed was 83.89%. For biodistribution studies, the rats were divided into two groups. Group I served as normal controls, while group II was subjected to carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (T) for induction of prostate carcinogenesis, which was confirmed histopathologically. The biodistribution studies on control and carcinogen-treated rats revealed a significant percent-specific uptake in prostate, which was found to be increased significantly as a function of time. The most significant finding of the study was an increase in the percent-specific uptake in prostate of carcinogen-treated animals when compared to the percent-specific uptake in prostate of normal rats after 2 and 4 hours postinjection. The study concludes that Tc-finasteride possesses selectively toward prostate cancer tissue and can be explored further for its role in detection of prostate cancer.
本研究旨在对新型5α-还原酶抑制剂非那雄胺进行放射性标记，以评估其在前列腺癌发生实验模型中的癌症靶向潜力。非那雄胺用锝有效地进行了放射性标记，标记效率>90%。发现该放射性药物在37°C的大鼠血清中6小时内稳定。锝-非那雄胺的血液动力学遵循双相释放模式，给药后15秒观察到快速释放期，30分钟后观察到缓慢释放期。观察到的放射性复合物的血浆蛋白结合率为83.89%。为进行生物分布研究，将大鼠分为两组。第一组作为正常对照组，第二组接受致癌物N-甲基-N-亚硝基脲（MNU）和激素丙酸睾酮（T）诱导前列腺癌发生，经组织病理学证实。对对照组和致癌物处理组大鼠的生物分布研究显示，前列腺中有显著的特异性摄取百分比，且发现其随时间显著增加。该研究最显著的发现是，与注射后2小时和4小时正常大鼠前列腺中的特异性摄取百分比相比，致癌物处理动物前列腺中的特异性摄取百分比有所增加。该研究得出结论，锝-非那雄胺对前列腺癌组织具有选择性，可进一步探索其在前列腺癌检测中的作用。
