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

• Type of Material: Article
• Authors: Shanshan Tan, Georgia State University; Hua Yang, Emory University; Shengui Xue, InLighta Biosci LLC; Jingjuan Qiao, Georgia State University; Mani Salarian, Georgia State University; Khan Hekmatyar, University of Georgia; Yuguang Meng, Emory University; Rao Mukkavilli, Georgia State University; Fan Pu, Georgia State University; Oluwatosin Y. Odubade, Georgia State University; Wayne Harris, Emory University; Yan Hai, Georgia State University; Melinda Yushak, Emory University; Vanessa M. Morales-Tirado, Univ Tennessee; Pardeep Mittal, Emory University; Phillip Zhe Sun, Emory University; David Lawson, Emory University; Hans Grossniklaus, Emory University
• Language: English
• Date: 2020-02-01
• Publisher: American Association ADVANCEMENT SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2020 The Authors
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1126/sciadv.aav7504
• Title of Journal or Parent Work: SCIENCE ADVANCES
• Volume: 6
• Issue: 6
• Start Page: eaav7504
• End Page: eaav7504
• Grant/Funding Information: This work was supported by NIH research grants (AA112713 and CA183376) to J.J.Y. and Georgia State University Brain & Behavior fellowship to S.T.
• Keywords: Science & Technology - Other Topics; CXCR4; EXPRESSION; UVEAL MELANOMA; PROGRESSION; Science & Technology; Multidisciplinary Sciences; OCULAR MELANOMA
• Research Categories: Health Sciences, Opthamology; Health Sciences, Oncology

Abstract

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 (r1 = 30.9 mM−1 s−1, r2 = 43.2 mM−1 s−1, 1.5 T; r1 = 23.5 mM−1 s−1, r2 = 98.6 mM−1 s−1, 7.0 T), strong CXCR4 binding (Kd = 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 mm3. Further development of the CXCR4-targeted imaging agent should have strong translation potential for early detection, surveillance, and treatment stratification of liver metastases patients.