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

Autor: Tan S; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA., Yang H; Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA., Xue S; InLighta Biosciences LLC, Atlanta, GA 30303, USA., Qiao J; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA., Salarian M; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA., Hekmatyar K; Bioimaging Research Center, University of Georgia, Athens, GA 30602, USA., Meng Y; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Mukkavilli R; Department of Biology, Georgia State University, Atlanta, GA 30303, USA., Pu F; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA., Odubade OY; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA., Harris W; Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA., Hai Y; Department of Mathematics and Statistics, Georgia State University, Atlanta, GA 30303, USA., Yushak ML; Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA., Morales-Tirado VM; Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38103, USA., Mittal P; Department of Radiology and Imaging, Augusta University, Augusta, GA 30912, USA., Sun PZ; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Lawson D; Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA., Grossniklaus HE; Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA., Yang JJ; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2020 Feb 07; Vol. 6 (6), pp. eaav7504. Date of Electronic Publication: 2020 Feb 07 (Print Publication: 2020).
DOI: 10.1126/sciadv.aav7504
Abstrakt: 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.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze: MEDLINE
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