title: Molecular imaging of tumor-infiltrating macrophages in a preclinical mouse model of breast cancer.
abstract: Significant evidence has indicated that tumor-associated macrophages (TAMs) play a critical role in the proliferation, invasion, angiogenesis, and metastasis of a variety of human carcinomas. In this study, we investigated whether near-infrared fluorescence (NIRF) imaging using a macrophage mannose receptor (MMR; CD206)-targeting agent could be used to noninvasively visualize and quantify changes in TAMs in vivo. The CD206-targeting NIRF agent, Dye-anti-CD206, was prepared and characterized in vitro and in vivo. By using NIRF imaging, we were able to noninvasively image tumor-infiltrating macrophages in the 4T1 mouse breast cancer model. Importantly, longitudinal NIRF imaging revealed the depletion of macrophages in response to zoledronic acid (ZA) treatment. However, ZA alone did not lead to the inhibition of 4T1 tumor growth. We therefore combined anti-macrophage ZA therapy and tumor cytotoxic docetaxel (DTX) therapy in the mouse model. The results demonstrated that this combination strategy could significantly inhibit tumor growth as well as tumor metastasis to the lungs. Based on these findings, we concluded that CD206-targeted molecular imaging can sensitively detect the dynamic changes in tumor-infiltrating macrophages, and that the combination of macrophage depletion and cytotoxic therapy is a promising strategy for the effective treatment of solid tumors.
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China;
authors.forename: Xianlei
authors.initials: X
authors.lastname: Sun
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China;
authors.forename: Duo
authors.initials: D
authors.lastname: Gao
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China;
authors.forename: Liquan
authors.initials: L
authors.lastname: Gao
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China;
authors.forename: Chenran
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China;
authors.forename: Xinhe
authors.initials: X
authors.lastname: Yu
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China;
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China; ; 2. Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China;
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000627:therapeutic use; D000077143:Docetaxel; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use; D037181:Lectins, C-Type / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000378:metabolism; D012680:Sensitivity and Specificity; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D043823:Taxoids / Q000627:therapeutic use; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid
keywords: CD206; Image-guided therapy.; Macrophage depletion; Optical imaging; Tumor-associated macrophage
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