title: A ¹¹C-labeled 1,4-dihydroquinoline derivative as a potential PET tracer for imaging of redox status in mouse brain.
abstract: A disturbance in redox balance has been implicated in the pathogenesis of a number of diseases. This study sought to examine the feasibility of imaging brain redox status using a (11)C-labeled dihydroquinoline derivative ([(11)C]DHQ1) for positron emission tomography (PET). The lipophilic PET tracer [(11)C]DHQ1 was rapidly oxidized to its hydrophilic form in mouse brain homogenate. The redox modulators diphenyleneiodonium and apocynin significantly reduced the initial velocity of [(11)C]DHQ1 oxidation, and apocynin also caused concentration-dependent inhibition of the initial velocity. Moreover, [(11)C]DHQ1 readily entered the brain by diffusion after administration and underwent oxidation into the hydrophilic cationic form, which then slowly decreased. By contrast, apocynin treatment inhibited the in vivo oxidation of [(11)C]DHQ1 to the hydrophilic cationic form, leading to a rapid decrease of radioactivity in the brain. Thus, the difference in the [(11)C]DHQ1 kinetics reflects the alteration in redox status caused by apocynin. In conclusion, [(11)C]DHQ1 is a potential PET tracer for imaging of redox status in the living brain.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Okada
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Wakizaka
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D049268:Positron-Emission Tomography / Q000379:methods*; D011804:Quinolines; D019275:Radiopharmaceuticals
chemical_list: C544515:1,4-dihydroquinoline; D000098:Acetophenones; D002250:Carbon Radioisotopes; D011804:Quinolines; D019275:Radiopharmaceuticals; C056165:acetovanillone