Shi Hui, Huttad Lakshmi Vageesh, Tan Mingdian, Liu Hongguang, Chua Mei-Sze, Cheng Zhen, So Samuel
Institute of Molecular Medicine, College of Life and Health Sciences, Northeastern University Shenyang 110000 China.
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University Stanford CA 94305 USA.
RSC Med Chem. 2021 Nov 23;13(1):90-97. doi: 10.1039/d1md00313e. eCollection 2022 Jan 27.
Liver cancer, of which hepatocellular carcinoma (HCC) is the most common form, is one of the most lethal cancers worldwide. The five-year survival rate for HCC is below 9%, which can be attributed to late diagnosis and limited treatment options at the late stage. Therefore, safe and efficient imaging strategies are urgently needed to facilitate HCC diagnosis and stage evaluation. The development of the second near infrared window (NIR-II, 1000-1700 nm) fluorescence imaging offers the advantages of enhanced resolutions, deeper penetration depth, and less autofluorescence compared to traditional NIR-I window (700-900 nm) imaging. Herein, an HCC targeted NIR-II fluorescent probe, GPC-ICG, was developed by labelling a humanized anti-GPC3 monoclonal antibody with indocyanine green (ICG). Compared to the negative control IgG-ICG probe, the GPC3-ICG probe demonstrated specific GPC3 targeting capability . And for GPC3 positive Huh-7 tumor bearing mice, the GPC3-ICG probe specifically accumulated in subcutaneous xenografts, with a tumor-background ratio (TBR) of up to 3. The NIR-II imaging of mice organs also indicated that GPC3-ICG specifically targeted Huh-7 tumor tissue. Overall, GPC3-ICG is a promising NIR-II probe for GPC3 targeted imaging of HCC.
肝癌,其中肝细胞癌(HCC)是最常见的形式,是全球最致命的癌症之一。HCC的五年生存率低于9%,这可归因于诊断延迟和晚期治疗选择有限。因此,迫切需要安全有效的成像策略来促进HCC的诊断和分期评估。与传统的近红外I窗口(700-900nm)成像相比,第二近红外窗口(NIR-II,1000-1700nm)荧光成像具有分辨率提高、穿透深度更深和自发荧光更少的优点。在此,通过用吲哚菁绿(ICG)标记人源化抗GPC3单克隆抗体,开发了一种靶向HCC的NIR-II荧光探针GPC-ICG。与阴性对照IgG-ICG探针相比,GPC3-ICG探针表现出特异性的GPC3靶向能力。对于GPC3阳性的荷Huh-7肿瘤小鼠,GPC3-ICG探针特异性积聚在皮下异种移植物中,肿瘤与背景比值(TBR)高达3。小鼠器官的NIR-II成像也表明GPC3-ICG特异性靶向Huh-7肿瘤组织。总体而言,GPC3-ICG是一种有前景的用于HCC的GPC3靶向成像的NIR-II探针。