Synthesis, Preclinical Evaluation, and First-in-Human Assessment of ICG-PSMA-D5: A PSMA-Targeted Probe for Fluorescence-Guided Surgery of Prostate Cancer

被引:0
作者
Chen, Yimin [1 ]
Liu, Wanjia [1 ]
Li, Ben [2 ]
Gao, Xi [1 ,3 ,4 ]
Zhou, Kaixiang [3 ,4 ]
Zhang, Mingxin [5 ]
Yang, Guangjie [2 ]
Cui, Mengchao [1 ,3 ,4 ]
机构
[1] Beijing Normal Univ, Coll Chem, Key Lab Radiopharmaceut, Minist Educ, Beijing 100875, Peoples R China
[2] Qingdao Univ, Affiliated Hosp, Dept Nucl Med, Qingdao 266000, Peoples R China
[3] Beijing Normal Univ Zhuhai, Ctr Adv Mat Res, Zhuhai 519087, Peoples R China
[4] Beijing Normal Univ Zhuhai, Fac Arts & Sci, Zhuhai 519087, Peoples R China
[5] Qingdao Univ, Affiliated Hosp, Dept Urol, Qingdao 266000, Peoples R China
基金
中国国家自然科学基金;
关键词
POSITIVE SURGICAL MARGINS; MEMBRANE ANTIGEN; RADICAL PROSTATECTOMY; IMAGING AGENTS; EXPRESSION; INHIBITOR;
D O I
10.1021/acs.jmedchem.4c02989
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Precise surgical resection of prostate cancer (PCa) is a significant clinical challenge due to the impact of positive surgical margins on postoperative outcomes. Fluorescence-guided surgery (FGS) enables real-time tumor visualization using fluorescent probes. In this study, we synthesized and evaluated an indocyanine green (ICG)-based PSMA-targeted near-infrared probe, ICG-PSMA-D5, for intraoperative imaging of PCa lesions. Spectroscopic analysis revealed that ICG-PSMA-D5 retained the optical properties of ICG while improving solubility in PBS due to additional carboxyl groups. In vitro assays demonstrated high binding affinity (K i = 0.39 nM) and minimal cytotoxicity. In vivo studies in tumor-bearing mice showed strong tumor targeting, extended retention at tumor site, and favorable biodistribution, with significant tumor-to-background ratios. The first-in-human study in a patient with localized PCa indicated the probe's potential for real-time, radiation-free surgical guidance. Overall, ICG-PSMA-D5 displayed excellent performance in tumor detection and margin delineation, making it a promising candidate for intraoperative FGS in PCa.
引用
收藏
页码:3858 / 3872
页数:15
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