RT Journal Article SR Electronic T1 Chemokine receptor 4 targeted protein MRI contrast agent for early detection of liver metastases JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaav7504 DO 10.1126/sciadv.aav7504 VO 6 IS 6 A1 Tan, Shanshan A1 Yang, Hua A1 Xue, Shenghui A1 Qiao, Jingjuan A1 Salarian, Mani A1 Hekmatyar, Khan A1 Meng, Yuguang A1 Mukkavilli, Rao A1 Pu, Fan A1 Odubade, Oluwatosin Y. A1 Harris, Wayne A1 Hai, Yan A1 Yushak, Melinda L. A1 Morales-Tirado, Vanessa M. A1 Mittal, Pardeep A1 Sun, Phillip Z. A1 Lawson, David A1 Grossniklaus, Hans E. A1 Yang, Jenny J. YR 2020 UL http://advances.sciencemag.org/content/6/6/eaav7504.abstract AB 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.