Muneer Ahamed, Daisy van Veghel, Christoph Ullmer, Koen Van Laere, Alfons Verbruggen, Guy M. Bormans
Abstract
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 (EC50 = 0.015 nM). MA2 and MA3 behaved as potent CB2 agonist (EC50: 3 nM and 0.1 nM, respectively) and their in vitro binding affinity for hCB2 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 EC50 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.
Pharmacology, Toxicology and Pharmaceutical Science
4
16%
Neuroscience
3
12%
Chemistry
2
8%
Nursing and Health Professions
1
4%
Computer Science
1
4%
Other
4
16%
Unknown
10
40%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 October 2016.
All research outputs
#17,285,036
of 25,373,627 outputs
Outputs from Frontiers in Neuroscience
#8,065
of 11,538 outputs
Outputs of similar age
#213,658
of 328,637 outputs
Outputs of similar age from Frontiers in Neuroscience
#83
of 131 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 131 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
