TY - JOUR
T1 - Chemokine receptor 4 targeted protein MRI contrast agent for early detection of liver metastases
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.
N1 - Funding Information:
We thank R. C. Long for operating the 4.7 T small-animal MRI scanner. We thank S. E. Woodman, T. A. McCannel, and B. L. Burgess for providing cell lines. We thank M. Kirberger for critical review and editing of this manuscript. We thank B. Canup for proofreading of this manuscript. We also thank Z. Liu, L. Yang, H. Mao, and A. Patel for helpful discussion on this project. This work was supported by NIH research grants (AA112713 and CA183376) to J.J.Y. and Georgia State University Brain & Behavior fellowship to S.T.
Publisher Copyright:
Copyright © 2020 The Authors,
PY - 2020/2/7
Y1 - 2020/2/7
N2 - 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.
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.
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U2 - 10.1126/sciadv.aav7504
DO - 10.1126/sciadv.aav7504
M3 - Article
C2 - 32083172
AN - SCOPUS:85079092091
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 6
M1 - eaav7504
ER -
