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Chimia (Aarau). 2014;68(4):208-10. doi: 10.2533/chimia.2014.208.

Development and evaluation of novel PET tracers for imaging cannabinoid receptor type 2 in brain.

Author information

  • 1ETH Zürich, Institute of Pharmaceutical Sciences Vladimir-Prelog-Weg 4 CH-8093 Zürich, Switzerland.
  • 2Muskelzentrum/ALS clinic Kantonsspital St. Gallen CH-9007 St. Gallen, Switzerland.
  • 3ETH Zürich, Institute of Pharmaceutical Sciences Vladimir-Prelog-Weg 4 CH-8093 Zürich, Switzerland. simon.ametamey@pharma.ethz.ch.
  • 4Department of Nuclear Medicine University Hospital Zürich CH-8091 Zürich;, Email: linjing.mu@usz.ch.

Abstract

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 [(11)C]KD2 exhibits superior properties. A pilot study using [(11)C]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 [(11)C]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.

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