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.