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′-[125I]iodophenyl)-3-methy-2-pyrazolin-5-one (125I-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, 125I-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/μmol, whereas the latter approach achieved specific activities of more than 0.14 GBq/μmol. On attempting to prepare an injectable formulation for 125I-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 125I-2 with low specific radioactivity into normal mice showed signs of distribution profiles similar to reported results for 14C-labeled edaravone in normal rats.
2010 The Pharmaceutical Society of Japan