11C Radiolabeling of anle253b: a Putative PET Tracer for Parkinson's Disease That Binds to α-Synuclein Fibrils in vitro and Crosses the Blood-Brain Barrier

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DOI

  • Andreas Maurer, University of Tübingen
  • ,
  • Andrei Leonov, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), MODAG GmbH
  • ,
  • Sergey Ryazanov, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute)
  • ,
  • Kristina Herfert, University of Tübingen
  • ,
  • Laura Kuebler, University of Tübingen
  • ,
  • Sabrina Buss, University of Tübingen
  • ,
  • Felix Schmidt, Ludwig-Maximilians-University München
  • ,
  • Daniel Weckbecker, Ludwig-Maximilians-University München
  • ,
  • Ruth Linder, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute)
  • ,
  • Dirk Bender
  • Armin Giese, Ludwig-Maximilians-University München, MODAG GmbH
  • ,
  • Bernd J. Pichler, University of Tübingen
  • ,
  • Christian Griesinger, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), MODAG GmbH

There is an urgent clinical need for imaging of α-synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bear potential for non-invasive detection of this biomarker in vivo. Here we demonstrate high-affinity binding of the family member anle253b to fibrillar αSyn and present a high-yielding site-selective radiosynthesis route for 11C radiolabeling using in-situ generated [11C]formaldehyde and reductive methylation. Radio-HPLC of the tracer after incubation with rat serum in vitro shows excellent stability of the molecule. Positron emission tomography in healthy animals is used to assess the pharmacokinetics and biodistribution of the tracer, showing good penetration of the blood–brain barrier and low background binding to the non-pathological brain.

OriginalsprogEngelsk
TidsskriftChemMedChem
Vol/bind15
Nummer5
Sider (fra-til)411-415
Antal sider5
ISSN1860-7179
DOI
StatusUdgivet - 5 mar. 2020

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