Journal Article In vivo evaluation of a new 18F-labeled PET ligand, [18F]FEBU, for the imaging of I2-imidazoline receptors

Kawamura, Kazunori  ,  Shimoda, Yoko  ,  Kumata, Katsushi  ,  Fujinaga, Masayuki  ,  Yui, Joji  ,  Yamasaki, Tomoteru  ,  Xie, Lin  ,  Hatori, Akiko  ,  Wakizaka, Hidekatsu  ,  Yusuke, Kurihara  ,  Ogawa, Masanao  ,  Nengaki, Nobuki  ,  Ming-Rong, Zhang

42 ( 4 )  , pp.406 - 412 , 2015-04 , Elsevier
Introduction: The functions of I2-imidazoline receptors (I2Rs) are unknown, but evidenceexists for their involvement in various neuropsychiatric disorders. Although a few positron emissiontomography (PET) I2R ligands have been developed, of which [11C]FTIMD and [11C]BU99008 wereevaluated as PET I2R imaging ligands in monkeys, no human PET imaging study using an I2R-selectivePET ligand has been conducted yet. Thus, we synthesized an 18F-labeled I2R-selective ligand(BU99018 or FEBU, Ki for I2Rs = 2.6 nM), and evaluated its application using rodents in PET imaging invivo toward the development of a clinically-useful I2R PET imaging ligand.Methods: [18F]FEBU was synthesized by the reaction of its precursor and [18F]fluoroethyl bromide. Abiodistribution and brain PET study were conducted in mice and rats, respectively.Results: [18F]FEBU was successfully synthesized, yielding a radioactivity suitable for injection (10.1 ±5.3% at the end of the irradiation (n = 10) based on 18F-). The specific activity at end of synthesis(EOS) was 40-147 TBq/mmol (n = 10). The radiochemical purity was >99% at EOS and remained>99% for 90 min after EOS. In mice, brain uptake was relatively high. In the blocking study with the coinjectionof the high-affinity I2R ligand BU224 (1 mg/kg b.w.), brain uptake was significantly decreased30 min post-injection. In the PET studies, the radioactivity was highly accumulated in the I2R-richhypothalamus. Pretreatment with BU224 (1 mg/kg b.w.) significantly decreased the radioactivity inthe hypothalamus to 23% of that of the control from 60 to 90 min post-injection.Conclusion: [18F]FEBU was sufficiently stable as a PET ligand and had a relatively high specific bindingaffinity for I2Rs in rats and mice.

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