趋化因子受体 4 靶向蛋白 MRI 对比剂用于肝转移的早期检测。

Chemokine receptor 4 targeted protein MRI contrast agent for early detection of liver metastases.

机构信息

Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.

Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA.

出版信息

Sci Adv. 2020 Feb 7;6(6):eaav7504. doi: 10.1126/sciadv.aav7504. eCollection 2020 Feb.

Liver metastases often progress from primary cancers including uveal melanoma (UM), breast, and colon cancer. Molecular biomarker imaging is a new non-invasive approach for detecting early stage tumors. Here, we report the elevated expression of chemokine receptor 4 (CXCR4) in liver metastases in UM patients and metastatic UM mouse models, and development of a CXCR4-targeted MRI contrast agent, ProCA32.CXCR4, for sensitive MRI detection of UM liver metastases. ProCA32.CXCR4 exhibits high relaxivities ( = 30.9 mM s, = 43.2 mM s, 1.5 T; = 23.5 mM s, = 98.6 mM s, 7.0 T), strong CXCR4 binding ( = 1.10 ± 0.18 μM), CXCR4 molecular imaging capability in metastatic and intrahepatic xenotransplantation UM mouse models. ProCA32.CXCR4 enables detecting UM liver metastases as small as 0.1 mm. Further development of the CXCR4-targeted imaging agent should have strong translation potential for early detection, surveillance, and treatment stratification of liver metastases patients.

肝转移通常由包括葡萄膜黑色素瘤（UM）、乳腺癌和结肠癌在内的原发性癌症发展而来。分子生物标志物成像技术是一种新的非侵入性方法，用于检测早期肿瘤。在这里，我们报告了趋化因子受体 4（CXCR4）在 UM 患者和转移性 UM 小鼠模型中的肝转移中的高表达，并开发了一种针对 CXCR4 的 MRI 对比剂 ProCA32.CXCR4，用于灵敏地检测 UM 肝转移。ProCA32.CXCR4 具有较高的弛豫率（ = 30.9 mM s， = 43.2 mM s，1.5 T； = 23.5 mM s， = 98.6 mM s，7.0 T），对 CXCR4 具有较强的结合能力（ = 1.10 ± 0.18 μM），并具有在转移性和肝内异种移植 UM 小鼠模型中进行 CXCR4 分子成像的能力。ProCA32.CXCR4 能够检测到小至 0.1 毫米的 UM 肝转移。进一步开发针对 CXCR4 的成像剂应该具有很强的转化潜力，用于早期检测、监测和治疗肝转移患者的分层。