1. Nucl Med Biol. 2009 May;36(4):455-65. Epub 2009 Mar 26.

Synthesis and biological evaluation of carbon-11- and fluorine-18-labeled
2-oxoquinoline derivatives for type 2 cannabinoid receptor positron emission
tomography imaging.

Evens N, Muccioli GG, Houbrechts N, Lambert DM, Verbruggen AM, Van Laere K,
Bormans GM.

Laboratory for Radiopharmacy, K.U. Leuven, 3000 Leuven, Belgium.

INTRODUCTION: The type 2 cannabinoid (CB(2)) receptor is part of the
endocannabinoid system and has been suggested as a mediator of several central
and peripheral inflammatory processes. Imaging of the CB(2) receptor has been
unsuccessful so far. We synthesized and evaluated a carbon-11- and a
fluorine-18-labeled 2-oxoquinoline derivative as new PET tracers with high
specificity and affinity for the CB(2) receptor. METHODS: Two 2-oxoquinoline
derivatives were synthesized and radiolabeled with either carbon-11 or
fluorine-18. Their affinity and selectivity for the human CB(2) receptor were
determined. Biological evaluation was done by biodistribution, radiometabolite
and autoradiography studies in mice. RESULTS: In vitro studies showed that both
compounds are high affinity CB(2)-specific inverse agonists. Biodistribution
study of the tracers in mice showed a high in vivo initial brain uptake and fast 
brain washout, in accordance with the low CB(2) receptor expression levels in
normal brain. A persistently high in vivo binding to the spleen was observed,
which was inhibited by pretreatment with two structurally unrelated CB(2)
selective inverse agonists. In vitro autoradiography studies with the
radioligands confirmed CB(2)-specific binding to the mouse spleen. CONCLUSION: We
synthesized two novel CB(2) receptor PET tracers that show high
affinity/selectivity for CB(2) receptors. Both tracers show favourable
characteristics as radioligands for central and peripheral in vivo visualization 
of the CB(2) receptor and are promising candidates for primate and human CB(2)
PET imaging.

PMID: 19423014 [PubMed - indexed for MEDLINE]