@article{oai:repo.qst.go.jp:00082825,
 author = {Yan, Xuefeng and Telu, Sanjay and M Dick, Rachel and Jeih-San, Liow and Paolo, Zanotti-Fregonara and L Morse, Cheryl and S Manly, Lester and L Gladding, Robert and Shrestha, Stal and Lerchner, Walter and Nagai, Yuji and Minamimoto, Takafumi and S Zoghbi, Sami and B Innis, Robert and W Pike, Victor and J Richmond, Barry and Ag Eldridge, Mark and Yuji, Nagai and Takafumi, Minamimoto},
 issue = {10},
 journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism},
 month = {Jan},
 note = {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.},
 pages = {2571--2581},
 title = {[11C]deschloroclozapine is an improved PET radioligand for quantifying a human muscarinic DREADD expressed in monkey brain.},
 volume = {41},
 year = {2021}
}