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

Shanshan Tan; Hua Yang; Shenghui Xue; Jingjuan Qiao; Mani Salarian; Khan Hekmatyar; Yuguang Meng; Rao Mukkavilli; Fan Pu; Oluwatosin Y. Odubade; Wayne Harris; Yan Hai; Melinda L. Yushak; Vanessa M. Morales-Tirado; Pardeep Mittal; Phillip Z. Sun; David Lawson; Hans E. Grossniklaus; Jenny J. Yang

doi:10.1126/sciadv.aav7504

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

Shanshan Tan, Hua Yang, Shenghui Xue, Jingjuan Qiao, Mani Salarian, Khan Hekmatyar, Yuguang Meng, Rao Mukkavilli, Fan Pu, Oluwatosin Y. Odubade, Wayne Harris, Yan Hai, Melinda L. Yushak, Vanessa M. Morales-Tirado, Pardeep Mittal, Phillip Z. Sun, David Lawson, Hans E. Grossniklaus, Jenny J. Yang

Diagnostic

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English (US)
Article number	eaav7504
Journal	Science Advances
Volume	6
Issue number	6
DOIs	https://doi.org/10.1126/sciadv.aav7504
State	Published - Feb 7 2020

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Tan, S., Yang, H., Xue, S., Qiao, J., Salarian, M., Hekmatyar, K., Meng, Y., Mukkavilli, R., Pu, F., Odubade, O. Y., Harris, W., Hai, Y., Yushak, M. L., Morales-Tirado, V. M., Mittal, P., Sun, P. Z., Lawson, D., Grossniklaus, H. E., & Yang, J. J. (2020). Chemokine receptor 4 targeted protein MRI contrast agent for early detection of liver metastases. Science Advances, 6(6), Article eaav7504. https://doi.org/10.1126/sciadv.aav7504

Tan, S, Yang, H, Xue, S, Qiao, J, Salarian, M, Hekmatyar, K, Meng, Y, Mukkavilli, R, Pu, F, Odubade, OY, Harris, W, Hai, Y, Yushak, ML, Morales-Tirado, VM, Mittal, P, Sun, PZ, Lawson, D, Grossniklaus, HE & Yang, JJ 2020, 'Chemokine receptor 4 targeted protein MRI contrast agent for early detection of liver metastases', Science Advances, vol. 6, no. 6, eaav7504. https://doi.org/10.1126/sciadv.aav7504

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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 (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.",

author = "Shanshan Tan and Hua Yang and Shenghui Xue and Jingjuan Qiao and Mani Salarian and Khan Hekmatyar and Yuguang Meng and Rao Mukkavilli and Fan Pu and Odubade, {Oluwatosin Y.} and Wayne Harris and Yan Hai and Yushak, {Melinda L.} and Morales-Tirado, {Vanessa M.} and Pardeep Mittal and Sun, {Phillip Z.} and David Lawson and Grossniklaus, {Hans E.} and Yang, {Jenny J.}",

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doi = "10.1126/sciadv.aav7504",

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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.

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

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