Target occupancy study and whole-body dosimetry with a MAGL PET ligand [¹¹C]PF-06809247 in non-human primates.

ABSTRACT:

Background

Monoacylglycerol lipase (MAGL) is a key serine hydrolase which terminates endocannabinoid signaling and regulates arachidonic acid driven inflammatory responses within the central nervous system. To develop [¹¹C]PF-06809247 into a clinically usable MAGL positron emission tomography (PET) radioligand, we assessed the occupancy of MAGL by an inhibitor in the non-human primate (NHP) brain. Additionally, we measured the whole-body distribution of [¹¹C]PF-06809247 in NHP and estimated human effective radiation doses.

Methods

Seven cynomolgus monkeys were enrolled for brain PET measurements. Two PET measurements along with arterial blood sampling were performed in each NHP: one baseline and one pretreatment condition with intravenous administration

SUBMITTER: Arakawa R 

PROVIDER: S-EPMC8897535 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature