Target occupancy study and whole-body dosimetry with a MAGL PET ligand [
MAGL
Non-human primate
Occupancy
PET
Radiation dose
Journal
EJNMMI research
ISSN: 2191-219X
Titre abrégé: EJNMMI Res
Pays: Germany
ID NLM: 101560946
Informations de publication
Date de publication:
04 Mar 2022
04 Mar 2022
Historique:
received:
13
07
2021
accepted:
25
01
2022
entrez:
4
3
2022
pubmed:
5
3
2022
medline:
5
3
2022
Statut:
epublish
Résumé
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 [ 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 of PF-06818883, a pro-drug of a selective MAGL inhibitor (total of seven doses between 0.01 and 1.27 mg/kg). Kinetic parameters K Radioactivity retention was decreased in all brain regions following pretreatment with PF-06818883. Occupancy was measured as 25.4-100.5% in a dose dependent manner. Whole-body PET showed high radioactivity uptake values in the liver, small intestine, kidney, and brain. The effective dose of [ [
Sections du résumé
BACKGROUND
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 [
METHODS
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 of PF-06818883, a pro-drug of a selective MAGL inhibitor (total of seven doses between 0.01 and 1.27 mg/kg). Kinetic parameters K
RESULTS
RESULTS
Radioactivity retention was decreased in all brain regions following pretreatment with PF-06818883. Occupancy was measured as 25.4-100.5% in a dose dependent manner. Whole-body PET showed high radioactivity uptake values in the liver, small intestine, kidney, and brain. The effective dose of [
CONCLUSIONS
CONCLUSIONS
[
Identifiants
pubmed: 35244788
doi: 10.1186/s13550-022-00882-2
pii: 10.1186/s13550-022-00882-2
pmc: PMC8897535
doi:
Types de publication
Journal Article
Langues
eng
Pagination
13Informations de copyright
© 2022. The Author(s).
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