Identification of the allosteric P2X7 receptor antagonist [11C]SMW139 as a PET tracer of microglial activation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-04-26

AUTHORS

Bieneke Janssen, Danielle J. Vugts, Shane M. Wilkinson, Dieter Ory, Sylvie Chalon, Jeroen J. M. Hoozemans, Robert C. Schuit, Wissam Beaino, Esther J. M. Kooijman, Johan van den Hoek, Mansoor Chishty, Aurélie Doméné, Anke Van der Perren, Alessandro Villa, Adriana Maggi, Ger T. Molenaar, Uta Funke, Rostislav V. Shevchenko, Veerle Baekelandt, Guy Bormans, Adriaan A. Lammertsma, Michael Kassiou, Albert D. Windhorst

ABSTRACT

The P2X7 receptor plays a significant role in microglial activation, and as a potential drug target, the P2X7 receptor is also an interesting target in positron emission tomography. The current study aimed at the development and evaluation of a potent tracer targeting the P2X7 receptor, to which end four adamantanyl benzamide analogues with high affinity for the human P2X7 receptor were labelled with carbon-11. All four analogues could be obtained in excellent radiochemical yield and high radiochemical purity and molar activity, and all analogues entered the rat brain. [11C]SMW139 showed the highest metabolic stability in rat plasma, and showed high binding to the hP2X7 receptor in vivo in a hP2X7 receptor overexpressing rat model. Although no significant difference in binding of [11C]SMW139 was observed between post mortem brain tissue of Alzheimer’s disease patients and that of healthy controls in in vitro autoradiography experiments, [11C]SMW139 could be a promising tracer for P2X7 receptor imaging using positron emission tomography, due to high receptor binding in vivo in the hP2X7 receptor overexpressing rat model. However, further investigation of both P2X7 receptor expression and binding of [11C]SMW139 in other neurological diseases involving microglial activation is warranted. More... »

PAGES

6580

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-24814-0

DOI

http://dx.doi.org/10.1038/s41598-018-24814-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103565883

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29700413


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