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Canna~Fangled Abstracts

Radiolabeling and in vitro / in vivo evaluation of N-(1-adamantyl)-8-methoxy-4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxamide as a PET probe for imaging cannabinoid type 2 receptor.

By June 26, 2013No Comments
pm2[Epub ahead of print]

Radiolabeling and in vitro / in vivo evaluation of N-(1-adamantyl)-8-methoxy-4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxamide as a PET probe for imaging cannabinoidtype 2 receptor.

Source

Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, Department of Nuclear Medicine, University Hospital Zürich, CH-8091, Zürich, Switzerland.

Abstract

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]
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