Development and Evaluation of Novel PET Tracers for Imaging Cannabinoid Receptor Type 2 in Brain
Keywords:Autoradiography, Cannabinoid receptor type 2 ligand, Neuroinflammation, Positron emission tomography, Radiolabeling
AbstractThe cannabinoid receptor type 2 (CB2) has a very low expression level in brain tissue under basal conditions, but it is up-regulated in diverse pathological conditions. Two promising lead structures from the literature, N-((3S,5S,7S)-adamantan-1-yl)-8-methoxy-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxamide and 8-butoxy-N-(2-fluoro-2-phenylethyl)-7-methoxy-2-oxo-1,2-dihydroquinoline-3-carboxamide – designated KD2 and KP23, respectively – were evaluated as potential PET ligands for imaging CB2. Both KD2 and KP23 were synthesized and labeled with carbon-11. In vitro autoradiographic studies on rodent spleen tissues showed that [11C]KD2 exhibits superior properties. A pilot study using [11C]KD2 on human post mortem ALS spinal cord slices indicated high CB2 expression level and specific binding, a very exciting finding if considering the future diagnostic application of CB2 ligands and their utility in therapy monitoring. In vivo blocking studies in rats with [11C]KD2 showed also high specific uptake in spleen tissue. Although the protein-bound fraction is relatively high, KD2 or KD2 derivatives could be very useful tools for the non-invasive investigation of CB2 levels under various neuroinflammatory conditions.
How to Cite
R. Slavik, D. Bieri, S. Čermak, A. Müller, S. D. Krämer, M. Weber, R. Schibli, S. M. Ametamey, L. Mu, Chimia 2014, 68, 208, DOI: 10.2533/chimia.2014.208.
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