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Title of Journal: Eur J Nucl Med Mol Imaging

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Abbravation: European Journal of Nuclear Medicine and Molecular Imaging

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Springer-Verlag

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DOI

10.1007/s10772-012-9149-1

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1619-7089

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Radioiodinated SB 207710 as a radioligand in vivo

Authors: Victor W Pike Christer Halldin Kenji Nobuhara Julka Hiltunen Rachel S Mulligan CarlGunnar Swahn Per Karlsson Hans Olsson Susan P Hume Ella Hirani Jaqueline Whalley Lyn S Pilowsky Stig Larsson PerOlof Schnell Peter J Ell Lars Farde
Publish Date: 2003/09/23
Volume: 30, Issue: 11, Pages: 1520-1528
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Abstract

Singlephoton emission tomography SPET and positron emission tomography PET when coupled to suitable radioligands are uniquely powerful for investigating the status of neurotransmitter receptors in vivo The serotonin subtype4 5HT4 receptor has discrete and very similar distributions in rodent and primate brain This receptor population may play a role in normal cognition and memory and is perhaps perturbed in some neuropsychiatric disorders SB 207710 1butyl4piperidinylmethyl8amino7iodo14benzodioxan5carboxylate is a selective highaffinity antagonist at 5HT4 receptors We explored radioiodinated SB 207710 as a possible radioligand for imaging 5HT4 receptors in vivo Rats were injected intravenously with iodine125 labelled SB 207710 euthanised at known times and dissected to establish radioactivity content in brain tissues Radioactivity entered brain but cleared rapidly and to a high extent from blood and plasma Between 45 and 75 min after injection the ratios of radioactivity concentration in each of 12 selected brain tissues to that in receptorpoor cerebellum correlated with previous measures of 5HT4 receptor density distribution in vitro The highest ratio was about 34 in striatum SB 207710 was labelled with iodine123 by an iododestannylation procedure A cynomolgus monkey was injected intravenously with 123ISB 207710 and examined by SPET Maximal whole brain uptake of radioactivity was 23 of the injected dose at 18 min after radioligand injection Brain images acquired between 9 and 90 min showed high radioactivity uptake in 5HT4 receptorrich regions such as striatum and low uptake in receptorpoor cerebellum At 169 min the ratio of radioactivity concentration in striatum to that in cerebellum was 40 In a second SPET experiment the cynomolgus monkey was pretreated with a selective 5HT4 receptor antagonist SB 204070 at 20 min before 123ISB 207710 injection Radioactivity in all brain regions was reduced almost to the level in cerebellum by 176 min after radioligand injection These findings show that 123ISB 207710 is an effective radioligand for imaging brain 5HT4 receptors in vivoThe authors are grateful to Drs L Gaster and AM Brown formerly of SmithKline Beecham Pharmaceuticals Harlow UK and now of GlaxoSmithKline Cambridge UK and Dr R Clark Roche Biosciences Palo Alto California USA for their interest in and support of this work and to SmithKline Beecham Pharmaceuticals for support to JW This work was also supported by grants from the Swedish Medical Research Council 03560 and 0914 the Swedish Natural Science Research Council KU 9973308 the USA National Institute of Mental Health NIMH 41205 and 44814 the SöderströmKönig Foundation and the Karolinska Institutet


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