PT - JOURNAL ARTICLE AU - Tan, Shanshan AU - Yang, Hua AU - Xue, Shenghui AU - Qiao, Jingjuan AU - Salarian, Mani AU - Hekmatyar, Khan AU - Meng, Yuguang AU - Mukkavilli, Rao AU - Pu, Fan AU - Odubade, Oluwatosin Y. AU - Harris, Wayne AU - Hai, Yan AU - Yushak, Melinda L. AU - Morales-Tirado, Vanessa M. AU - Mittal, Pardeep AU - Sun, Phillip Z. AU - Lawson, David AU - Grossniklaus, Hans E. AU - Yang, Jenny J. TI - Chemokine receptor 4 targeted protein MRI contrast agent for early detection of liver metastases AID - 10.1126/sciadv.aav7504 DP - 2020 Feb 01 TA - Science Advances PG - eaav7504 VI - 6 IP - 6 4099 - http://advances.sciencemag.org/content/6/6/eaav7504.short 4100 - http://advances.sciencemag.org/content/6/6/eaav7504.full SO - Sci Adv2020 Feb 01; 6 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.