Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P21554 (
cannabinoid receptor
)
3,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The type 2
cannabinoid receptor
(CB2) is a member of the endocannabinoid system and is known for its important role in (neuro)inflammation. A PET-imaging agent that allows
in vivo
visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and
in vitro
evaluation of a carbon-11 ([
11
C]MA2) and a fluorine-18 ([
18
F]
MA3
) labeled analog of a highly potent
N
-arylamide oxadiazole CB2 agonist (EC
50
= 0.015 nM). MA2 and
MA3
behaved as potent CB2 agonist (EC
50
: 3 nM and 0.1 nM, respectively) and their
in vitro
binding affinity for
h
CB2 was found to be 87 nM and 0.8 nM, respectively. Also
MA3
(substituted with a fluoro ethyl group) was found to have higher binding affinity and EC
50
values when compared to the originally reported trifluoromethyl analog
12
. [
11
C]MA2 and [
18
F]
MA3
were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [
11
C]MA2 and [
18
F]
MA3
are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for
in vivo
imaging of brain CB2 receptors. However, in view of its higher affinity and selectivity, further detailed evaluation of
MA3
as a PET tracer for CB2 is warranted.
...
PMID:Synthesis, Biodistribution and
In vitro
Evaluation of Brain Permeable High Affinity Type 2 Cannabinoid Receptor Agonists [
11
C]MA2 and [
18
F]MA3. 2771 86
