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Identification of the allosteric P2X receptor antagonist [C]SMW139 as a PET tracer of microglial activation. | LitMetric

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Article Abstract

The P2X receptor plays a significant role in microglial activation, and as a potential drug target, the P2X 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 P2X receptor, to which end four adamantanyl benzamide analogues with high affinity for the human P2X 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. [C]SMW139 showed the highest metabolic stability in rat plasma, and showed high binding to the hP2X receptor in vivo in a hP2X receptor overexpressing rat model. Although no significant difference in binding of [C]SMW139 was observed between post mortem brain tissue of Alzheimer's disease patients and that of healthy controls in in vitro autoradiography experiments, [C]SMW139 could be a promising tracer for P2X receptor imaging using positron emission tomography, due to high receptor binding in vivo in the hP2X receptor overexpressing rat model. However, further investigation of both P2X receptor expression and binding of [C]SMW139 in other neurological diseases involving microglial activation is warranted.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920098PMC
http://dx.doi.org/10.1038/s41598-018-24814-0DOI Listing

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