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11 C 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
Author(s) -
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.,
Griesinger Christian
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900689
Subject(s) - chemistry , blood–brain barrier , biodistribution , radiosynthesis , spect imaging , biomarker , in vitro , in vivo , positron emission tomography , parkinson's disease , fibril , imaging agent , biophysics , biochemistry , pathology , nuclear medicine , biology , medicine , neuroscience , disease , genetics , central nervous system
Abstract 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 11 C radiolabeling using in‐situ generated [ 11 C]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.