title: Kit formulation for preparation and biological evaluation of a novel (99m)Tc-oxo complex with metronidazole xanthate for imaging tumor hypoxia.
abstract: BACKGROUND
  Achieving an ideal (99m)Tc labeled nitroimidazole hypoxia marker is still considered to be of great interest. Metronidazole xanthate (MNXT) ligand was synthesized and radiolabeled with (99m)Tc-glucoheptonate (GH) to form the (99m)TcO-MNXT complex, for the potential use as a novel probe for imaging tumor hypoxia.
  
  
  METHODS
  For labeling, (99m)TcO-MNXT was prepared by ligand-exchange reaction with (99m)Tc-GH. The radiochemical purity of the (99m)TcO-MNXT complex was measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The distribution coefficient and stability of the complex was investigated. The structure of the (99m)TcO-MNXT complex was verified by preparation and characterization of the corresponding stable rhenium complex. The cellular uptake of the (99m)TcO-MNXT complex was determined in murine sarcoma S180 cell lines under hypoxic and aerobic conditions. The biodistribution and single photon emission computed tomography (SPECT) image studies of the (99m)TcO-MNXT complex were performed in mice bearing S 180 tumor.
  
  
  RESULTS
  The radiochemical purity of the (99m)TcO-MNXT complex was over 90%. It had good in vitro stability and its distribution coefficient indicated that it was a hydrophilic complex. When (99m)Tc and Re complexes were coinjected in HPLC, both radioactivity (for (99m)Tc complex) and UV detectors (for Re complex) showed nearly identical HPLC profiles, suggesting their structures are similar. The tumor cell experiment and the biodistribution in mice bearing S 180 tumor showed that the (99m)TcO-MNXT complex had a good hypoxic selectivity and accumulated in the tumor with high uptake and good retention. Single photon emission computed tomography (SPECT) image studies showed that the tumor detection was observable.
  
  
  CONCLUSIONS
  (99m)TcO-MNXT is prepared from a kit without the need for purification and shows high tumor uptake, tumor/blood and tumor/muscle ratios, suggesting that it would be a promising candidate for imaging tumor hypoxia.
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, P.R. China.
authors.forename: Zhenxiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, P.R. China. Electronic address: zhjunbo@bnu.edu.cn.
authors.forename: Junbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, P.R. China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nuclear Medicine Department, Peking University 3rd Hospital, Beijing 100191, P.R. China. Electronic address: jinzhonghui@163.com.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Nuclear Medicine Department, Peking University 3rd Hospital, Beijing 100191, P.R. China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Nuclear Medicine Department, Peking University 3rd Hospital, Beijing 100191, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000737:chemistry*; D051379:Mice; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D011854:Radiochemistry; D012509:Sarcoma / Q000000981:diagnostic imaging / Q000473:pathology*; D013400:Sugar Acids / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D015609:Organotechnetium Compounds; D013400:Sugar Acids; C000611952:technetium 99m oxobis(metronidazole xanthate); D008795:Metronidazole; C007852:alpha-glucoheptonic acid
keywords: (99m)Tc; Hypoxia; Imaging; Metronidazole; Tumor; Xanthate