文章：

使用与钆偶联的嵌合抗Glypican-3抗体的磁共振成像在体外和体内选择性检测Glypican-3阳性肝细胞癌

Magnetic Resonance Imaging Using a Chimeric Anti-Glypican-3 Antibody Conjugated with Gadolinium Selectively Detects Glypican-3-Positive Hepatocellular Carcinoma In Vitro and In Vivo

原文发布日期：17 October 2025

DOI: 10.3390/cancers17203357

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Glypican-3 (GPC3) is a cell surface oncofetal protein that is highly expressed in hepatocellular carcinoma (HCC) but absent in normal liver tissue, making it an attractive target for molecularly targeted diagnosis and therapy. To support GPC3-targeted treatment strategies, there is a need for a non-invasive imaging tool capable of detecting GPC3-positive tumors.Methods: We conjugated a commercially available murine anti-GPC3 antibody (1G12), or a proprietary chimeric anti-GPC3 antibody (ET58) to the standard magnetic resonance imaging (MRI) contrast agent, gadolinium, via a DOTA chelator. The resulting probes, 1G12-DOTA-Gd or ET58-DOTA-Gd, respectively, were assessed for in vitro relaxivity and binding specificity to GPC3-positive HCC cells, as well as for in vivo imaging performance in mouse xenograft models bearing GPC3-positive or GPC3-negative HCC tumors.Conclusions: ET58-DOTA-Gd shows high specificity, imaging efficacy, and a favorable immunogenicity profile, thereby making it a promising candidate for clinical translation as a GPC3-targeted MRI probe. It holds potential as a non-invasive companion diagnostic for identifying GPC3-positive HCC patients who may benefit from GPC3-targeted therapies.

摘要翻译： 

背景/目的：磷脂酰肌醇蛋白聚糖-3（GPC3）是一种细胞表面癌胚蛋白，在肝细胞癌（HCC）中高表达，但在正常肝组织中不表达，这使其成为分子靶向诊断和治疗的有吸引力的靶点。为支持GPC3靶向治疗策略，需要一种能够检测GPC3阳性肿瘤的非侵入性成像工具。 方法：我们通过DOTA螯合剂将市售鼠源抗GPC3抗体（1G12）或专有的嵌合抗GPC3抗体（ET58）与标准磁共振成像（MRI）造影剂钆偶联。分别评估所得探针1G12-DOTA-Gd和ET58-DOTA-Gd的体外弛豫率、对GPC3阳性HCC细胞的结合特异性，以及在携带GPC3阳性或GPC3阴性HCC肿瘤的小鼠异种移植模型中的体内成像性能。 结论：ET58-DOTA-Gd显示出高特异性、成像效果良好且免疫原性较低，因此有望作为GPC3靶向MRI探针进行临床转化。它具备作为非侵入性伴随诊断工具的潜力，可用于识别可能受益于GPC3靶向治疗的GPC3阳性HCC患者。

原文链接：

Magnetic Resonance Imaging Using a Chimeric Anti-Glypican-3 Antibody Conjugated with Gadolinium Selectively Detects Glypican-3-Positive Hepatocellular Carcinoma In Vitro and In Vivo