Development and Evaluation of Novel 68Ga/177Lu-Labeled PSMA Inhibitors with Enhanced Pharmacokinetics and Tumor Imaging for Prostate Cancer

被引：0
作者：
Li, Haiyang [1 ,2 ,4 ]
Liu, Yang [1 ,2 ,3 ]
Yuan, Hongmei [1 ,2 ,4 ]
Cai, Ping [1 ,2 ,4 ]
Wu, Tongtong [1 ,2 ,4 ]
Yang, Zhicong [1 ,2 ,4 ]
Nie, Jiaqi [1 ,2 ,4 ]
Zhang, Wei [5 ]
Huang, Zhanwen [1 ,2 ,3 ]
Liu, Nan [5 ]
Chen, Yue [1 ,2 ,3 ]
Zhou, Zhijun [1 ,2 ,3 ,4 ]
机构：
[1] Southwest Med Univ, Affiliated Hosp, Dept Nucl Med, Luzhou 646000, Sichuan, Peoples R China
[2] Nucl Med & Mol Imaging Key Lab Sichuan Prov, Luzhou 646000, Sichuan, Peoples R China
[3] Southwest Med Univ, Inst Nucl Med, Luzhou 646000, Sichuan, Peoples R China
[4] Southwest Med Univ, Sch Pharm, Dept Pharmaceut, Luzhou 646000, Sichuan, Peoples R China
[5] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Nucl Med, Chengdu 610072, Sichuan, Peoples R China
来源：
MOLECULAR PHARMACEUTICS | 2025年 / 22卷 / 03期
基金：
中国国家自然科学基金;
关键词：
positron emission tomography (PET); Ga-68/Lu-177; prostate-specific membrane antigen (PSMA); prostate cancer; polyethylene glycol (PEG); MEMBRANE ANTIGEN;
D O I：
10.1021/acs.molpharmaceut.4c01302
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Prostate-specific membrane antigen (PSMA) has been a key target for diagnosing and treating prostate cancer, particularly in high-grade, metastatic, and therapy-resistant tumors. This study presents a series of novel Ga-68- and Lu-177-labeled PSMA inhibitors, derived from the previously developed [Ga-68]Ga-Flu-1. We explored the impact of PEG chains, lipophilic macrocycles, and dimerization on their in vivo properties. The Ga-68- and Lu-177-labeled inhibitors were assessed for biodistribution and tumor targeting in PC3-PIP tumor xenografts, leading to the identification of several promising candidates based on imaging and tumor-specific uptake. Positron emission tomography (PET) imaging revealed that the poly(ethylene glycol)-modified [Ga-68]Ga-BisPSMA-P4 demonstrated rapid tumor penetration and excellent tumor-to-background contrast. In comparative biodistribution studies, the naphthalene ring-modified [Ga-68]Ga-BisPSMA-Nph-P4 showed higher tumor uptake (similar to 60% ID/g at 1 h postinjection) and rapid renal clearance (similar to 25% ID/g at 2 h postinjection). Additionally, [Lu-177]Lu-BisPSMA-Nph-P4 displayed superior retention, with significant uptake on day 7, highlighting its potential as a novel PSMA inhibitor for prostate cancer diagnosis and treatment.
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页码：1584 / 1597
页数：14
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