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

Maurer, Andreas; Leonov, Andrei; Ryazanov, Sergey; Herfert, Kristina; Kuebler, Laura; Buss, Sabrina; Schmidt, Felix; Weckbecker, Daniel; Linder, Ruth; Bender, Dirk; Giese, Armin; Pichler, Bernd J. und Griesinger, Christian (2020): C-11 Radiolabeling of anle253b: a Putative PET Tracer for Parkinson's Disease That Binds to alpha-Synuclein Fibrils in vitro and Crosses the Blood-Brain Barrier. In: Chemmedchem, Bd. 15, Nr. 5: S. 411-415

Abstract

There is an urgent clinical need for imaging of alpha-synuclein (alpha Syn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of alpha Syn are rare. Diphenyl pyrazoles are known modulators of alpha Syn 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 alpha Syn and present a high-yielding site-selective radiosynthesis route for C-11 radiolabeling using in-situ generated [C-11]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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1860-7179
• Sprache: Englisch