Selective binding of 2-[125I]iodo-nisoxetine to norepinephrine transporters in the brain

Nuclear Medicine and Biology
Mei-Ping KungHank F Kung

Abstract

A radioiodinated ligand, (R)-N-methyl-(2-[(125)I]iodo-phenoxy)-3-phenylpropylamine, [(125)I]2-INXT, targeting norepinephrine transporters (NET), was successfully prepared. A no-carrier-added product, [(125)I]2-INXT, displayed a saturable binding with a high affinity (K(d)=0.06 nM) in the homogenates prepared from rat cortical tissues as well as from LLC-PK(1) cells expressing NET. A relatively low number of binding sties (B(max)=55 fmol/mg protein) measured with [(125)I]2-INXT in rat cortical homogenates is consistent with the value reported for a known NET ligand, [(3)H]nisoxetine. Competition studies with various compounds on [(125)I]2-INXT binding clearly confirmed the pharmacological specificity and selectivity for NET binding sites. Following a tail-vein injection of [(125)I]2-INXT in rats, a good initial brain uptake was observed (0.56% dose at 2 min) followed by a slow washout from the brain (0.2% remained at 3 hours post-injection). The hypothalamus (a NET-rich region) to striatum (a region devoid of NET) ratio was 1.5 at 3 hours post-i.v. injection. Pretreatment of rats with nisoxetine significantly inhibited the uptake of [(125)I]2-INXT (70-100% inhibition) in locus coeruleus, hypothalamus and raphe nuclei, regions kn...Continue Reading

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Citations

Mar 9, 2006·European Journal of Nuclear Medicine and Molecular Imaging·Naoki KanegawaHideo Saji
Oct 23, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Annette Beatrix BrühlUwe Herwig
Mar 5, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Anne Marie D AxelHenrik H Hansen
May 25, 2006·Nuclear Medicine and Biology·William C EckelmanChester A Mathis
Mar 21, 2006·Nuclear Medicine and Biology·William C Eckelman, Chester A Mathis
Oct 26, 2005·Nuclear Medicine and Biology·Yu-Shin Ding, Joanna Fowler
Jul 17, 2013·Nuclear Medicine and Biology·Laetitia LemoineHank F Kung
Oct 9, 2013·Nuclear Medicine and Biology·Christina Rami-MarkWolfgang Wadsak
May 3, 2011·Nuclear Medicine and Biology·Adriana Alexandre S TavaresSally L Pimlott
Feb 13, 2010·The International Journal of Neuropsychopharmacology·Bruno P GuiardPierre Blier
Jan 26, 2013·Laboratory Animals·Aage Kristian Olsen Alstrup, Donald F Smith
May 25, 2010·Journal of Labelled Compounds & Radiopharmaceuticals·Vivien L NguyenJogeshwar Mukherjee

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