| Autor: |
Pike, Victor W., Halldin, Christer, McCarron, Julie A., Lundkvist, Camilla, Hirani, Ella, Olsson, Hans, Hume, Susan P., Karlsson, Per, Osman, Safiye, Swahn, Carl-Gunnar, Hall, Håkan, Wikström, Håkan, Mensonidas, Marguerite, Poole, Keith G., Farde, Lars |
| Předmět: |
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| Zdroj: |
European Journal of Nuclear Medicine; 1998, Vol. 25 Issue 4, p338-346, 9p |
| Abstrakt: |
Abstract. [carbonyl-[sup 11]C]Desmethyl-WAY-100635 (DWAY) is possibly a low-level metabolite appearing in plasma after intravenous administration of [carbonyl[sup 11]C]WAY-100635 to human subjects for positron emission tomographic (PET) imaging of brain 5-HT[sub 1A] receptors. In this study we set out to assess the ability of DWAY to enter brain in vivo and to elucidate its possible interaction with 5-HT[sub 1A] receptors. Desmethyl-WAY-100635 was labelled efficiently with carbon-11 (t[sub 1/2] = 20.4 min) in high specific radioactivity by reaction of its descyclohexanecarbonyl analogue with [carbonyl[sup 11]C]cyclohexanecarbonyl chloride. The product was separated in high radiochemical purity by high-performance liquid chromatography (HPLC) and formulated for intravenous injection. Rats were injected intravenously with DWAY, sacrificed at known times and dissected to establish radioactivity content in brain tissues. At 60 min alter injection, the ratios of radioactivity concentration in each brain region to that in cerebellum correlated with previous in vitro and in vivo measures of 5-HT[sub 1A] receptor density. The highest ratio was about 22 in hippocampus. Radioactivity cleared rapidly from plasma; HPLC analysis revealed that DWAY represented 55% of the radioactivity in plasma at 5 min and 33% at 30 min. Only polar radioactive metabolites were detected. Subsequently, a cynomolgus monkey was injected intravenously with DWAY and examined by PET. Maximal whole brain uptake of radioactivity was 5.7% of the administered dose at 5 min after injection. The image acquired between 9 and 90 min showed high radioactivity uptake in brain regions rich in 5-HT[sub 1A] receptors (e.g. frontal cortex and neocortex), moderate uptake in raphe nuclei and low uptake in cerebellum. A transient equilibrium was achieved in cortical regions at about 60 min, when the ratio of radioactivity concentration in frontal cortex to that in cerebellum reached 6. The corresponding ratio for raph [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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