The CB₂ receptor plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease and is therefore a very promising target for therapeutic approaches as well as for imaging. Based on the literature, we identified one 4-oxoquinoline derivative (designated KD2) as the lead structure. It was synthesized, radiolabeled and evaluated as a potential imaging tracer for CB₂ . [¹¹ C]KD2 was obtained in 99% radiochemical purity. Moderate blood-brain barrier passage was predicted for KD2 from an in vitro transport assay with P-glycoprotein-transfected MDCK cells. No efflux of KD2 by P-glycoprotein was detected. In vitro autoradiography of rat and mouse spleen slices demonstrated that [¹¹C]KD2 exhibits high specific binding towards CB₂ . High spleen uptake of [¹¹ C]KD2 was observed in dynamic PET studies with Wistar rats and its specificity was confirmed by displacement study with a selective CB₂agonist, GW405833. A pilot autoradiography study with post mortem spinal cord slices from ALS patients with [¹¹C]KD2 suggested the presence of CB₂ receptors under disease conditions. Specificity of [¹¹ C]KD2 binding could also be demonstrated on these human tissues. In conclusion, [¹¹ C]KD2 shows good in vitro and in vivo properties as a potential PET tracer for CB₂ . This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.

PMID:

 

23795580

 

[PubMed – as supplied by publisher]