title: A Functional CT Contrast Agent for In Vivo Imaging of Tumor Hypoxia.
abstract: Hypoxia, which has been well established as a key feature of the tumor microenvironment, significantly influences tumor behavior and treatment response. Therefore, imaging for tumor hypoxia in vivo is warranted. Although some imaging modalities for detecting tumor hypoxia have been developed, such as magnetic resonance imaging, positron emission tomography, and optical imaging, these technologies still have their own specific limitations. As computed tomography (CT) is one of the most useful imaging tools in terms of availability, efficiency, and convenience, the feasibility of using a hypoxia-sensitive nanoprobe (Au@BSA-NHA) for CT imaging of tumor hypoxia is investigated, with emphasis on identifying different levels of hypoxia in two xenografts. The nanoprobe is composed of Au nanoparticles and nitroimidazole moiety which can be electively reduced by nitroreductase under hypoxic condition. In vitro, Au@BSA-NHA attain the higher cellular uptake under hypoxic condition. Attractively, after in vivo administration, Au@BSA-NHA can not only monitor the tumor hypoxic environment with CT enhancement but also detect the hypoxic status by the degree of enhancement in two xenograft tumors with different hypoxic levels. The results demonstrate that Au@BSA-NHA may potentially be used as a sensitive CT imaging agent for detecting tumor hypoxia.
authors.affiliation: Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No.197, RuiJin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: The Education Ministry Key Laboratory of Resource Chemistry, Department of Chemistry, Life and Environmental Science College, Shanghai Normal University, No.100, Guilin Road, Shanghai, 200234, P. R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The Education Ministry Key Laboratory of Resource Chemistry, Department of Chemistry, Life and Environmental Science College, Shanghai Normal University, No.100, Guilin Road, Shanghai, 200234, P. R. China.
authors.forename: Chusen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Radiology, Jing'an District Center Hospital, No.259, Xikang Road, Shanghai, 200040, P. R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gu
authors.affiliation: The Education Ministry Key Laboratory of Resource Chemistry, Department of Chemistry, Life and Environmental Science College, Shanghai Normal University, No.100, Guilin Road, Shanghai, 200234, P. R. China.
authors.forename: Ti
authors.initials: T
authors.lastname: Jia
authors.affiliation: The Education Ministry Key Laboratory of Resource Chemistry, Department of Chemistry, Life and Environmental Science College, Shanghai Normal University, No.100, Guilin Road, Shanghai, 200234, P. R. China.
authors.forename: Amin
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No.197, RuiJin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No.197, RuiJin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No.197, RuiJin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Xianfu
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No.197, RuiJin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: The Education Ministry Key Laboratory of Resource Chemistry, Department of Chemistry, Life and Environmental Science College, Shanghai Normal University, No.100, Guilin Road, Shanghai, 200234, P. R. China.
authors.forename: Nengqin
authors.initials: N
authors.lastname: Jia
authors.affiliation: Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No.197, RuiJin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Miao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D005354:Fibrosarcoma / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed / Q000379:methods*; D000072258:Tumor Hypoxia / Q000502:physiology*
chemical_list: D003287:Contrast Media
keywords: computed tomography; contrast agent; gold nanoparticles; hypoxia; nanoprobes