title: 1-(3'-[125I]Iodophenyl)-3-methy-2-pyrazolin-5-one: preparation, solution stability, and biodistribution in normal mice.
abstract: 3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone, 1), known as a potent free radical scavenger, has been developed as a medical drug for the treatment of acute cerebral infarction. With the aim of developing radiotracers for imaging free radicals in vivo, 1-(3'-[(125)I]iodophenyl)-3-methy-2-pyrazolin-5-one ((125)I-2) was synthesized by two methods, via isotopic exchange and interhalogen exchange under solvent-free conditions, in which iodo- and bromo-derivatives were used as labeling precursors, respectively. After HPLC purification, (125)I-2 was obtained in modest isolated radiochemical yields (ca. 20%) with high radiochemical purities by both methods. The former gave specific activities of 0.2-0.6 kBq/micromol, whereas the latter approach achieved specific activities of more than 0.14 GBq/micromol. On attempting to prepare an injectable formulation for (125)I-2 with high specific activity, its radiochemical purities dropped to about 60-70%. Unlabeled analog 2 was found to have lipophilic and antioxidant properties similar to edaravone. Intravenous injection of (125)I-2 with low specific radioactivity into normal mice showed signs of distribution profiles similar to reported results for (14)C-labeled edaravone in normal rats.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Yuuhei
authors.initials: Y
authors.lastname: Sano
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Motomura
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yamamoto
authors.forename: Miki
authors.initials: M
authors.lastname: Fukuda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Minoru
authors.initials: M
authors.lastname: Maeda
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D000077553:Edaravone; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D047069:Pyrazolones / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility; D014018:Tissue Distribution
chemical_list: C553882:1-(3'-iodophenyl)-3-methy-2-pyrazolin-5-one; D000975:Antioxidants; D047069:Pyrazolones; D000077553:Edaravone; D000983:Antipyrine