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", 
    "description": "<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>", 
    "language": "eng", 
    "title": "Identification of the allosteric P2X7 receptor antagonist [11C]SMW139 as a PET tracer of microglial activation.", 
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        "title": "Imaging of Neuroinflammation in Neurodegenerative Diseases", 
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    "publication_date": "2018-04-26", 
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        "orcid": "0000-0001-9573-8558", 
        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.", 
        "name": "Janssen, Bieneke"
      }, 
      {
        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.", 
        "name": "Vugts, Danielle J"
      }, 
      {
        "affiliation": "School of Chemistry, University of Sydney, Sydney, Australia.", 
        "name": "Wilkinson, Shane M"
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        "affiliation": "Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.", 
        "name": "Ory, Dieter"
      }, 
      {
        "affiliation": "UMR 1253, iBrain, Universit\u00e9 de Tours, Inserm, Tours, France.", 
        "name": "Chalon, Sylvie"
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      {
        "affiliation": "Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.", 
        "name": "Hoozemans, Jeroen JM"
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      {
        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.", 
        "name": "Schuit, Robert C"
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        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.", 
        "name": "Beaino, Wissam"
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      {
        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.", 
        "name": "Kooijman, Esther JM"
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      {
        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.", 
        "name": "van den Hoek, Johan"
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      {
        "affiliation": "Pharmidex Pharmaceutical Services Ltd., London, United Kingdom.", 
        "name": "Chishty, Mansoor"
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      {
        "affiliation": "UMR 1253, iBrain, Universit\u00e9 de Tours, Inserm, Tours, France.", 
        "name": "Dom\u00e9n\u00e9, Aur\u00e9lie"
      }, 
      {
        "affiliation": "Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium.", 
        "name": "Van der Perren, Anke"
      }, 
      {
        "orcid": "0000-0002-7445-916X", 
        "affiliation": "Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.", 
        "name": "Villa, Alessandro"
      }, 
      {
        "affiliation": "Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.", 
        "name": "Maggi, Adriana"
      }, 
      {
        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands and BV Cyclotron VU, Amsterdam, The Netherlands.", 
        "name": "Molenaar, Ger T"
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        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium and BV Cyclotron VU, Amsterdam, The Netherlands.", 
        "name": "Funke, Uta"
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        "affiliation": "Pharmidex Pharmaceutical Services Ltd., London, United Kingdom.", 
        "name": "Shevchenko, Rostislav V"
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        "affiliation": "Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium.", 
        "name": "Baekelandt, Veerle"
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        "affiliation": "Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.", 
        "name": "Bormans, Guy"
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        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.", 
        "name": "Lammertsma, Adriaan A"
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        "affiliation": "School of Chemistry, University of Sydney, Sydney, Australia.", 
        "name": "Kassiou, Michael"
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        "orcid": "0000-0002-1250-7656", 
        "affiliation": "Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.", 
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