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

Autor: Kawamura K; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan. Electronic address: kawamur@nirs.go.jp., Shimoda Y; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan., Kumata K; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan., Fujinaga M; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan., Yui J; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan., Yamasaki T; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan., Xie L; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan., Hatori A; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan., Wakizaka H; Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan., Kurihara Y; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan; SHI Accelerator Service Ltd., Tokyo 141-0032, Japan., Ogawa M; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan; SHI Accelerator Service Ltd., Tokyo 141-0032, Japan., Nengaki N; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan; SHI Accelerator Service Ltd., Tokyo 141-0032, Japan., Zhang MR; Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Jazyk: angličtina
Zdroj: Nuclear medicine and biology [Nucl Med Biol] 2015 Apr; Vol. 42 (4), pp. 406-12. Date of Electronic Publication: 2014 Dec 26.
DOI: 10.1016/j.nucmedbio.2014.12.014
Abstrakt: 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 [(11)C]FTIMD and [(11)C]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 (18)F-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: [(18)F]FEBU was synthesized by the reaction of its precursor and [(18)F]fluoroethyl bromide. A biodistribution and brain PET study were conducted in mice and rats respectively.
Results: [(18)F]FEBU was successfully synthesized yielding a radioactivity suitable for injection (10.1 ± 5.3% at the end of the irradiation (n=10) based on (18)F(-)). 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 co-injection 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: [(18)F]FEBU was sufficiently stable as a PET ligand and had a relatively high specific binding affinity for I₂Rs in rats and mice.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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