title: Synthesis and biodistribution of a novel (⁹⁹m)TcN complex of norfloxacin dithiocarbamate as a potential agent for bacterial infection imaging.
abstract: Achieving a (⁹⁹m)Tc-labeled fluoroquinolone derivative as a single photon emission computed tomography (SPECT) tracer is considered to be of great interest. The norfloxacin dithiocarbamate (NFXDTC) was synthesized and radiolabeled with a [(⁹⁹m)TcN]²(+) intermediate to form the (⁹⁹m)TcN-NFXDTC complex in high yield. The radiochemical purity of (⁹⁹m)TcN-NFXDTC was over 90%, as measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), without any notable decomposition at room temperature over a period of 6 h. The partition coefficient and electrophoresis results indicated that (⁹⁹m)TcN-NFXDTC was lipophilic and neutral. The bacterial binding assay studies showed tht (⁹⁹m)TcN-NFXDTC had a good binding affinity. Biodistribution results in bacterial infected mice showed that (⁹⁹m)TcN-NFXDTC had a higher uptake at the sites of infection and better abscess/blood and abscess/muscle ratios than those of (⁹⁹m)Tc-ciprofloxacin and (⁹⁹m)TcN-CPFXDTC (CPFXDTC = ciprofloxacin dithiocarbamate). The biodistribution results of (⁹⁹m)TcN-NFXDTC in bacterially infected mice and in mice with turpentine-induced abscesses indicated that (⁹⁹m)TcN-NFXDTC was suited to be a bacteria-specific infection imaging agent. Single photon emission computed tomography (SPECT) image studies showed there was a visible accumulation in infection sites, suggesting that it would be a promising candidate for bacterial infection imaging.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.
authors.forename: Shijian
authors.initials: S
authors.lastname: Zhang
authors.forename: Weifang
authors.initials: W
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Jin
authors.forename: Xuebin
authors.initials: X
authors.lastname: Wang
authors.forename: Junbo
authors.initials: J
authors.lastname: Zhang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000000981:diagnostic imaging*; D004355:Drug Stability; D004590:Electrophoresis, Paper; D007249:Inflammation / Q000000981:diagnostic imaging; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D051379:Mice; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000737:chemistry*; D011817:Rabbits; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D008024:Ligands; D015609:Organotechnetium Compounds; C558921:norfloxacin dithiocarbamate; D009643:Norfloxacin