دورية أكاديمية
Synthesis, characterization, and monkey positron emission tomography (PET) studies of [18F]Y1-973, a PET tracer for the neuropeptide Y Y1 receptor.
| العنوان: | Synthesis, characterization, and monkey positron emission tomography (PET) studies of [18F]Y1-973, a PET tracer for the neuropeptide Y Y1 receptor. |
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| المؤلفون: | Hostetler ED; Imaging, Merck Research Laboratories, West Point, PA 19486, USA. eric_hostetler@merck.com, Sanabria-Bohórquez S, Fan H, Zeng Z, Gantert L, Williams M, Miller P, O'Malley S, Kameda M, Ando M, Sato N, Ozaki S, Tokita S, Ohta H, Williams D, Sur C, Cook JJ, Burns HD, Hargreaves R |
| المصدر: | NeuroImage [Neuroimage] 2011 Feb 14; Vol. 54 (4), pp. 2635-42. Date of Electronic Publication: 2010 Nov 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 9215515 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9572 (Electronic) Linking ISSN: 10538119 NLM ISO Abbreviation: Neuroimage Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Orlando, FL : Academic Press, c1992- |
| مواضيع طبية MeSH: | Brain/*diagnostic imaging , Fluorine Radioisotopes/*pharmacokinetics , Radiopharmaceuticals/*chemical synthesis , Radiopharmaceuticals/*pharmacokinetics , Receptors, Neuropeptide Y/*biosynthesis, Animals ; Autoradiography ; Humans ; Macaca mulatta ; Positron-Emission Tomography ; Radioactive Tracers |
| مستخلص: | Neuropeptide Y receptor subtype 1 (NPY Y1) has been implicated in appetite regulation, and antagonists of NPY Y1 are being explored as potential therapeutics for obesity. An NPY Y1 PET tracer is useful for determining the level of target engagement by NPY Y1 antagonists in preclinical and clinical studies. Here we report the synthesis and evaluation of [(18)F]Y1-973, a novel PET tracer for NPY Y1. [(18)F]Y1-973 was radiolabeled by reaction of a primary chloride with [(18)F]KF/K2.2.2 followed by deprotection with HCl. [(18)F]Y1-973 was produced with high radiochemical purity (>98%) and high specific activity (>1000 Ci/mmol). PET studies in rhesus monkey brain showed that the distribution of [(18)F]Y1-973 was consistent with the known NPY Y1 distribution; uptake was highest in the striatum and cortical regions and lowest in the pons, cerebellum nuclei, and brain stem. Blockade of [(18)F]Y1-973 uptake with NPY Y1 antagonist Y1-718 revealed a specific signal that was dose-dependently reduced in all regions of grey matter to a similarly low level of tracer uptake, indicative of an NPY Y1 specific signal. In vitro autoradiographic studies with [(18)F]Y1-973 in rhesus monkey and human brain tissue slices revealed an uptake distribution consistent with the in vivo PET studies. Highest binding density was observed in the dentate gyrus, caudate-putamen, and cortical regions; moderate binding density in the hypothalamus and thalamus; and lowest binding density in the globus pallidus and cerebellum. In vitro saturation binding studies in rhesus monkey and human caudate-putamen homogenates confirmed a similarly high B(max)/K(d) ratio for [(18)F]Y1-973, suggesting the tracer may provide a specific signal in human brain of similar magnitude to that observed in rhesus monkey. [(18)F]Y1-973 is a suitable PET tracer for imaging NPY Y1 in rhesus monkey with potential for translation to human PET studies. (Copyright © 2010 Elsevier Inc. All rights reserved.) |
| المشرفين على المادة: | 0 (Fluorine Radioisotopes) 0 (Radioactive Tracers) 0 (Radiopharmaceuticals) 0 (Receptors, Neuropeptide Y) 0 (neuropeptide Y-Y1 receptor) |
| تواريخ الأحداث: | Date Created: 20101117 Date Completed: 20110502 Latest Revision: 20161125 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.neuroimage.2010.11.014 |
| PMID: | 21078401 |
| قاعدة البيانات: | MEDLINE |
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