Journal article Open Access

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

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


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{
  "DOI": "10.1038/s41598-018-24814-0", 
  "container_title": "Scientific Reports", 
  "language": "eng", 
  "title": "Identification of the allosteric P2X7 receptor antagonist [11C]SMW139 as a PET tracer of microglial activation.", 
  "issued": {
    "date-parts": [
      [
        2018, 
        4, 
        26
      ]
    ]
  }, 
  "abstract": "<p><strong>Abstract</strong></p>\n\n<p>The P2X<sub>7</sub> receptor plays a significant role in microglial activation, and as a potential drug target, the P2X<sub>7</sub> 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<sub>7</sub> receptor, to which end four adamantanyl benzamide analogues with high affinity for the human P2X<sub>7</sub> 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. [<sup>11</sup>C]SMW139 showed the highest metabolic stability in rat plasma, and showed high binding to the hP2X<sub>7</sub> receptor in vivo in a hP2X<sub>7</sub> receptor overexpressing rat model. Although no significant difference in binding of [<sup>11</sup>C]SMW139 was observed between post mortem brain tissue of Alzheimer&#39;s disease patients and that of healthy controls in in vitro autoradiography experiments, [<sup>11</sup>C]SMW139 could be a promising tracer for P2X<sub>7</sub> receptor imaging using positron emission tomography, due to high receptor binding in vivo in the hP2X<sub>7</sub> receptor overexpressing rat model. However, further investigation of both P2X<sub>7</sub> receptor expression and binding of [<sup>11</sup>C]SMW139 in other neurological diseases involving microglial activation is warranted.</p>", 
  "author": [
    {
      "family": "Janssen, Bieneke"
    }, 
    {
      "family": "Vugts, Danielle J"
    }, 
    {
      "family": "Wilkinson, Shane M"
    }, 
    {
      "family": "Ory, Dieter"
    }, 
    {
      "family": "Chalon, Sylvie"
    }, 
    {
      "family": "Hoozemans, Jeroen JM"
    }, 
    {
      "family": "Schuit, Robert C"
    }, 
    {
      "family": "Beaino, Wissam"
    }, 
    {
      "family": "Kooijman, Esther JM"
    }, 
    {
      "family": "van den Hoek, Johan"
    }, 
    {
      "family": "Chishty, Mansoor"
    }, 
    {
      "family": "Dom\u00e9n\u00e9, Aur\u00e9lie"
    }, 
    {
      "family": "Van der Perren, Anke"
    }, 
    {
      "family": "Villa, Alessandro"
    }, 
    {
      "family": "Maggi, Adriana"
    }, 
    {
      "family": "Molenaar, Ger T"
    }, 
    {
      "family": "Funke, Uta"
    }, 
    {
      "family": "Shevchenko, Rostislav V"
    }, 
    {
      "family": "Baekelandt, Veerle"
    }, 
    {
      "family": "Bormans, Guy"
    }, 
    {
      "family": "Lammertsma, Adriaan A"
    }, 
    {
      "family": "Kassiou, Michael"
    }, 
    {
      "family": "Windhorst, Albert D"
    }
  ], 
  "page": "6580", 
  "volume": "8", 
  "type": "article-journal", 
  "issue": "1", 
  "id": "1298620"
}
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