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(68)Ga 标记的靶向 CSPG4 肽用于胰腺癌和胃癌 PET/CT 成像的临床前评价

英文原题:Preclinical Evaluation of (68)Ga-Labeled CSPG4-Targeting Peptides for PET/CT Imaging in Pancreatic and Gastric Carcinoma.

PubMed 2025/10/15(内容时间) J Med Chem Q1 · IF 7.3(JCR 2025)

研究概要

在胰腺癌(ASPC1)和胃癌(MKN45)模型中,[68Ga]Ga-DOTA-TH10显示出显著的肿瘤摄取(ASPC1:60 min时为1.63 ± 0.15%ID/g),并通过Western blot和免疫组化证实CSPG4过表达而得到验证。

中文摘要

硫酸软骨素蛋白聚糖4(CSPG4)在多种实体瘤中高表达,并促进肿瘤进展和迁移。靶向CSPG4的治疗,如单克隆抗体9.2.27和CAR-M,已进入临床试验。数据库分析进一步将CSPG4水平升高与两种癌症的总生存期降低相关联。实现多种实体瘤中异常CSPG4表达的实时可视化仍是一个亟待解决的关键问题。为解决这一问题,我们率先制备了三种靶向CSPG4的68 Ga标记PET探针,[ 68 Ga]Ga-DOTA-LS10、[ 68 Ga]Ga-DOTA-SH11和[ 68 Ga]Ga-DOTA-TH10。在胰腺癌(ASPC1)和胃癌(MKN45)模型中,[ 68 Ga]Ga-DOTA-TH10显示出显著的肿瘤摄取(ASPC1:60 min时为1.63 ± 0.15%ID/g),并通过Western blot和免疫组织化学证实CSPG4过表达。本研究首次使用68 Ga标记肽对胰腺癌和胃癌模型中的CSPG4表达进行PET成像,旨在为其表达的临床实时监测提供指导。

展开英文摘要原文

Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed in various solid tumors and promotes tumor progression and migration. Targeting CSPG4 therapy, such as monoclonal antibodies 9.2.27 and CAR-M, has already been in clinical trials. Database analysis further correlated elevated levels of CSPG4 with reduced overall survival in both cancers. Achieving real-time visualization of aberrant CSPG4 expression in various solid tumors remains a critical issue that needs to be addressed. To address this, we pioneered the preparation of three 68 Ga-labeled PET probes targeting CSPG4, [ 68 Ga]Ga-DOTA-LS10, [ 68 Ga]Ga-DOTA-SH11, and [ 68 Ga]Ga-DOTA-TH10. In pancreatic (ASPC1) and gastric (MKN45) carcinoma models, [ 68 Ga]Ga-DOTA-TH10 showed prominent tumor uptake (ASPC1:1.63 ± 0.15%ID/g at 60 min), validated by Western blot and immunohistochemistry confirming CSPG4 overexpression. This study conducted the first PET imaging on CSPG4 expression in pancreatic cancer and gastric cancer models using 68 Ga-labeled peptides, aiming to provide guidance for clinical real-time monitoring of its expression.

论文信息

作者
Wang Z、Pan X、Li Y、Zhang F、Bian L、Li J
单位
Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.China
期刊
Journal of medicinal chemistry2025 Nov 13
原文标识
PubMed 41088886 · DOI 10.1021/acs.jmedchem.5c02187