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- Title
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.
- Authors
Mu, Linjing; Bieri, Daniel; Slavik, Roger; Drandarov, Konstantin; Müller, Adrienne; Čermak, Stjepko; Weber, Markus; Schibli, Roger; Krämer, Stefanie D.; Ametamey, Simon M.
- Abstract
The cannabinoid type 2 (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. [11C] KD2 was obtained in 99% radiochemical purity. Moderate blood-brain barrier ( BBB) passage was predicted for KD2 from an in vitro transport assay with P-glycoprotein-transfected Madin Darby canine kidney 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 [11C] KD2 was observed in dynamic positron emission tomography (PET) studies with Wistar rats and its specificity was confirmed by displacement study with a selective CB2 agonist, GW405833. A pilot autoradiography study with post-mortem spinal cord slices from amyotrophic lateral sclerosis ( ALS) patients with [11C] KD2 suggested the presence of CB2 receptors under disease conditions. Specificity of [11C] KD2 binding could also be demonstrated on these human tissues. In conclusion, [11C] KD2 shows good in vitro and in vivo properties as a potential PET tracer for CB2.
- Subjects
AMYOTROPHIC lateral sclerosis; POSITRON emission; NEUROMUSCULAR diseases; NEURODEGENERATION; AUTORADIOGRAPHY
- Publication
Journal of Neurochemistry, 2013, Vol 126, Issue 5, p616
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.12354