title: Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers.
abstract: The imaging of hypoxia is important for therapeutic decision making in various diseases. (68)Ga is an important radionuclide for positron emission tomography (PET), and its usage is increasing, due to the development of the (68)Ge/(68)Ga-generator. In the present study, the authors synthesized two nitroimidazole derivatives by conjugating nitroimidazole and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an amide bond (4) and a thiourea bond (5). Both derivatives were labeled with (68)Ga with high labeling efficiency and were stable after labeling. The low partition coefficients (logP) of (68)Ga-4 (-4.6) and (68)Ga-5 (-4.5) demonstrated the hydrophilic natures of the derivatives, and both showed higher uptake in cancer cell lines cultured under hypoxic condition than under normoxic condition. However, (68)Ga-5 showed higher liver uptake than (68)Ga-4 in a biodistribution study due to higher lipophilicity. In an animal PET study, (68)Ga-4 showed higher standard uptake values (SUV) in tumors than (68)Ga-5 in mice xenografted with CT-26 mouse colon cancer cells.
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Lathika
authors.initials: L
authors.lastname: Hoigebazar
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Mee Kyung
authors.initials: MK
authors.lastname: Hong
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Ji Youn
authors.initials: JY
authors.lastname: Lee
authors.forename: Dinesh
authors.initials: D
authors.lastname: Shetty
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: D000818:Animals; D016466:CHO Cells; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006367:HeLa Cells; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid