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.