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

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 (r(1) = 30.9 mM(−1) s(−1), r(2) = 43.2 mM(−1) s(−1), 1.5 T; r(1) = 23.5 mM(−1) s(−1), r(2) = 98.6 mM(−1) s(−1), 7.0 T), strong CXCR4 binding (K(d) = 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(3). Further development of the CXCR4-targeted imaging agent should have strong translation potential for early detection, surveillance, and treatment stratification of liver metastases patients.