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[11C]deschloroclozapine is an improved PET radioligand for quantifying a human muscarinic DREADD expressed in monkey brain.
https://repo.qst.go.jp/records/82825
https://repo.qst.go.jp/records/828250ab72345-6684-4c56-b2db-fb95c7cca4e6
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-05-13 | |||||
タイトル | ||||||
タイトル | [11C]deschloroclozapine is an improved PET radioligand for quantifying a human muscarinic DREADD expressed in monkey brain. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Yan, Xuefeng
× Yan, Xuefeng× Telu, Sanjay× M Dick, Rachel× Jeih-San, Liow× Paolo, Zanotti-Fregonara× L Morse, Cheryl× S Manly, Lester× L Gladding, Robert× Shrestha, Stal× Lerchner, Walter× Nagai, Yuji× Minamimoto, Takafumi× S Zoghbi, Sami× B Innis, Robert× W Pike, Victor× J Richmond, Barry× Ag Eldridge, Mark× Yuji, Nagai× Takafumi, Minamimoto |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Previous work found that [C]deschloroclozapine ([C]DCZ) is superior to [C]clozapine ([C]CLZ) for imaging Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). This study used PET to quantitatively and separately measure the signal from transfected receptors, endogenous receptors/targets, and non-displaceable binding in other brain regions to better understand this superiority. A genetically-modified muscarinic type-4 human receptor (hMDi) was injected into the right amygdala of a male rhesus macaque. [C]DCZ and [C]CLZ PET scans were conducted 2-24 months later. Uptake was quantified relative to the concentration of parent radioligand in arterial plasma at baseline (n = 3 scans/radioligand) and after receptor blockade (n = 3 scans/radioligand). Both radioligands had greater uptake in the transfected region and displaceable uptake in other brain regions. Displaceable uptake was not uniformly distributed, perhaps representing off-target binding to endogenous receptor(s). After correction, [C]DCZ signal was 19% of that for [C]CLZ, and background uptake was 10% of that for [C]CLZ. Despite stronger [C]CLZ binding, the signal-to-background ratio for [C]DCZ was almost two-fold greater than for [C]CLZ. Both radioligands had comparable DREADD selectivity. All reference tissue models underestimated signal-to-background ratio in the transfected region by 40%-50% for both radioligands. Thus, the greater signal-to-background ratio of [C]DCZ was due to its lower background uptake. | |||||
書誌情報 |
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 巻 41, 号 10, p. 2571-2581, 発行日 2021-01 |
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出版者 | ||||||
出版者 | SAGE Publications | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0271-678X | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 33853405 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1177/0271678X211007949 | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://journals.sagepub.com/doi/full/10.1177/0271678X211007949 |