engleski

Development and Evaluation of Novel PET Tracers for Imaging Cannabinoid Receptor Type 2 in Brain

The 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.

autoradiography; cannabinoid receptor type 2 ligand; neuroinflammation; positron emission tomography; radiolabeling

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