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


Slavik, Roger; Bieri, Daniel; Cermak, Stjepko; Müller, Adrienne; Krämer, Stefanie D; Weber, Markus; Schibli, Roger; Ametamey, Simon M; Mu, Linjing (2014). Development and evaluation of novel PET tracers for imaging cannabinoid receptor type 2 in brain. CHIMIA International Journal for Chemistry, 68(4):208-210.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2014
Deposited On:20 Feb 2015 11:37
Last Modified:05 Apr 2016 19:06
Publisher:Swiss Chemical Society
ISSN:0009-4293
Additional Information:Copyright ©Swiss Chemical Society: CHIMIA, Volume 68, Number 4, April 2014, pp. 208-210(3)
Publisher DOI:https://doi.org/10.2533/chimia.2014.208
PubMed ID:24983598

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