title: Syntheses of 2-nitroimidazole derivatives conjugated with 1,4,7-triazacyclononane-N,N'-diacetic acid labeled with F-18 using an aluminum complex method for hypoxia imaging.
abstract: Hypoxia imaging is important for diagnosis of ischemic diseases, and thus various (18)F-labeled radiopharmaceuticals have been developed. However, (18)F-labeling requires multistep procedures including azeotropic distillation, which is complicated and difficult to automate. Recently, (18)F-labeling method using Al-F complex in aqueous solution was devised that offered a straightforward (18)F-labeling procedure. We synthesized nitroimidazole derivatives conjugated with 1,4,7-triazacyclononane-1,4-diacetic acid (NODA) that can be labeled with (18)F using Al-F complex and examined their radiochemistries, in vitro and in vivo biological properties, and animal PET imaging characteristics. We found that the synthesized derivatives have excellent (18)F-labeling efficiencies, high stabilities, specific uptakes in cultured hypoxic tumor cells, and high tumor to nontumor ratios in xenografted mice. Furthermore, the derivatives were labeled with (18)F in a straightforward manner within 15 min at high labeling efficiencies and radiochemical purities. In conclusion, (18)F-labeled NODA-nitroimidazole conjugates were developed and proved to be promising hypoxia PET agents.
authors.affiliation: Radiation Applied Life Sciences, Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: Lathika
authors.initials: L
authors.lastname: Hoigebazar
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Lee
authors.forename: Dinesh
authors.initials: D
authors.lastname: Shetty
authors.forename: Bo Yeun
authors.initials: BY
authors.lastname: Yang
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Lee
mesh_terms: D000535:Aluminum; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006224:Cricetinae; D003412:Cricetulus; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000378:metabolism; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: C519451:1,4,7-triazacyclononane-1,4-diacetate; D001798:Blood Proteins; D056831:Coordination Complexes; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; D007093:Imidazoles; D009574:Nitro Compounds; D019275:Radiopharmaceuticals; D000535:Aluminum