[11C]deschloroclozapine is an improved PET radioligand for quantifying a human muscarinic DREADD expressed in monkey brain
In: Journal of Cerebral Blood Flow & Metabolism, Jg. 41 (2021-04-14), S. 2571-2582
Online
unknown
Zugriff:
Previous work found that [11C]deschloroclozapine ([11C]DCZ) is superior to [11C]clozapine ([11C]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 (hM4Di) was injected into the right amygdala of a male rhesus macaque. [11C]DCZ and [11C]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, [11C]DCZ signal was 19% of that for [11C]CLZ, and background uptake was 10% of that for [11C]CLZ. Despite stronger [11C]CLZ binding, the signal-to-background ratio for [11C]DCZ was almost two-fold greater than for [11C]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 [11C]DCZ was due to its lower background uptake.
Titel: |
[11C]deschloroclozapine is an improved PET radioligand for quantifying a human muscarinic DREADD expressed in monkey brain
|
---|---|
Autor/in / Beteiligte Person: | Nagai, Yuji ; Zoghbi, Sami S. ; Lerchner, Walter ; Gladding, Robert L. ; Lester S Manly ; Liow, Jeih-San ; Mark A.G. Eldridge ; Shrestha, Stal ; Minamimoto, Takafumi ; Rachel M Dick ; Richmond, Barry J. ; Zanotti-Fregonara, Paolo ; Yan, Xuefeng ; Morse, Cheryl L. ; Pike, Victor W. ; Telu, Sanjay ; Innis, Robert B. |
Link: | |
Zeitschrift: | Journal of Cerebral Blood Flow & Metabolism, Jg. 41 (2021-04-14), S. 2571-2582 |
Veröffentlichung: | SAGE Publications, 2021 |
Medientyp: | unknown |
ISSN: | 1559-7016 (print) ; 0271-678X (print) |
DOI: | 10.1177/0271678x211007949 |
Schlagwort: |
|
Sonstiges: |
|