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

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 (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 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.