Synthesis and Evaluation of Radioligands for Imaging Brain Nociceptin/Orphanin FQ Peptide (NOP) Receptors with Positron Emission Tomography
| العنوان: | Synthesis and Evaluation of Radioligands for Imaging Brain Nociceptin/Orphanin FQ Peptide (NOP) Receptors with Positron Emission Tomography |
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| المؤلفون: | Victor W. Pike, Vanessa N. Barth, Masahiro Fujita, Concepción Pedregal, Jinsoo Hong, Zhaogen Chen, Robert B. Innis, Nuria Diaz, Karen S. Rash, Michael A. Statnick, Yasuyuki Kimura, Johannes Tauscher, Miguel A. Toledo, Sami S. Zoghbi, Susan L. Gackenheimer |
| المصدر: | Journal of Medicinal Chemistry. 54:2687-2700 |
| بيانات النشر: | American Chemical Society (ACS), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Magnetic Resonance Spectroscopy, NOP, Pharmacology, Article, Radioligand Assay, Tandem Mass Spectrometry, Drug Discovery, medicine, Radioligand, Animals, Receptor, Opioid peptide, medicine.diagnostic_test, Chemistry, Brain, Stereoisomerism, Haplorhini, Rats, Nociceptin receptor, Opioid Peptides, Positron emission tomography, Positron-Emission Tomography, Molecular Medicine, Ex vivo, Chromatography, Liquid |
| الوصف: | Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by (11)C-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [(11)C](S)-10a-c, gave similar results. Baseline scans showed high entry of radioactivity into the brain to give a distribution reflecting that expected for NOP receptors. Preblock experiments showed high early peak levels of brain radioactivity, which rapidly declined to a much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [(11)C](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation in human subjects. |
| تدمد: | 1520-4804 0022-2623 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::58cb4463f6c5c583d1ef38934f7f769aTest https://doi.org/10.1021/jm101487vTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....58cb4463f6c5c583d1ef38934f7f769a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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