کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2154802 | 1090252 | 2006 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand](/preview/png/2154802.png)
چکیده انگلیسی
The potent histamine H3 receptor antagonist JNJ-10181457 (1) was successfully labeled with 11C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28±8%) and high specific radioactivity (56±26 GBq/μmol). The binding of [11C]1 to H3 receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [11C]1 in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H3 antagonists, JNJ-5207852 (2) and unlabeled Compound (1), in a concentration-dependent manner. The biodistribution of [11C]1 in rats was measured at 5, 10, 30 and 60 min. The uptake of [11C]1 in regions rich in H3 receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [11C]1 in the rat brain could not be blocked by pretreatment with either Compound (2) (30 min or 24 h pretreatment) or cold Compound (1) (30-min pretreatment). The biodistribution of [11C]1 in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H3(â/â) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [11C]1 could not specifically label H3 receptors in rodent brain in vivo. Possible causes are discussed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nuclear Medicine and Biology - Volume 33, Issue 6, August 2006, Pages 801-810
Journal: Nuclear Medicine and Biology - Volume 33, Issue 6, August 2006, Pages 801-810
نویسندگان
Anu J. Airaksinen, Jill A. Jablonowski, Margreet van der Mey, Ann J. Barbier, Rob P. Klok, Joost Verbeek, Robert Schuit, Jacobus D.M. Herscheid, Josee E. Leysen, Nicholas I. Carruthers, Adriaan A. Lammertsma, Albert D. Windhorst,