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

Abstract：

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.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Kawamura K,Shimoda Y,Kumata K,Fujinaga M,Yui J,Yamasaki T,Xie L,Hatori A,Wakizaka H,Kurihara Y,Ogawa M,Nengaki N,Zhang MR

doi

10.1016/j.nucmedbio.2014.12.014

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

406-12

issue

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(14)00579-4

journal_volume

pub_type

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