title: CXCR4-targeted near-infrared imaging allows detection of orthotopic and metastatic human osteosarcoma in a mouse model.
abstract: CXCR4 is expressed at primary and metastatic sites of osteosarcoma. We developed a novel CXCR4-targeted near-infrared (NIR) fluorescent imaging agent (referred to as CXCR4-IR-783). The binding to representative osteosarcoma cells (F5M2 and F4 for high- and low- CXCR4 expression) was examined. CXCR4-IR-783 fluorescence was also examined in a mouse xenograft model of human osteosarcoma using NIR fluorescence microscopy and a Kodak in-vivo multispectral system. Pulmonary metastases in mice bearing osteosarcoma xenografts were detected by micro CT, (18)F-PET scan and NIR imaging scan. Briefly, the binding of CXCR4-IR-783 was significantly higher in F5M2 than in F4 cells. Intense NIR fluorescence signals were detected in osteosarcoma xenografts, with signal/background ratio at 4.87 in mice bearing the F5M2 cell. At 4 weeks after F5M2 cell inoculation, metastatic lesions in the lungs were detectable using CXCR4-IR-783 and micro-CT scan, but not with (18)F-FDG PET scan. In conclusion, CXCR4-IR-783 is a promising tool for detection of high CXCR4-expressing osteosarcoma, and particularly for its metastatic lesions.
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.|Department of Microsurgery, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Guan
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Microsurgery, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Health Management, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Lianjia
authors.initials: L
authors.lastname: Yang
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Radiology, Division of Molecular Imaging, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Radiology, Division of Molecular Imaging, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Ran
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Radiology, Division of Molecular Imaging, Baylor College of Medicine, Houston, Texas 77030, USA.|Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston, School of Public Health, Houston, Texas 77030, USA.
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
authors.affiliation: Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D061848:Optical Imaging; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014183:Transplantation, Heterologous; D055114:X-Ray Microtomography
chemical_list: D019718:Receptors, CXCR4