量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Introduction: The functions of I2-imidazoline receptors (I2Rs) are unknown, but evidence
exists for their involvement in various neuropsychiatric disorders. Although a few positron emission
tomography (PET) I2R ligands have been developed, of which [11C]FTIMD and [11C]BU99008 were
evaluated as PET I2R imaging ligands in monkeys, no human PET imaging study using an I2R-selective
PET 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 in
vivo 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. A
biodistribution 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 coinjection
of the high-affinity I2R ligand BU224 (1 mg/kg b.w.), brain uptake was significantly decreased
30 min post-injection. In the PET studies, the radioactivity was highly accumulated in the I2R-rich
hypothalamus. Pretreatment with BU224 (1 mg/kg b.w.) significantly decreased the radioactivity in
the 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 binding
affinity for I2Rs in rats and mice.
In vivo evaluation of a new 18F-labeled PET ligand, [18F]FEBU, for the imaging of I2-imidazoline receptors
