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.
Andreas MaurerAndrei LeonovSergey RyazanovKristina HerfertLaura KueblerSabrina BussFelix SchmidtDaniel WeckbeckerRuth LinderDirk BenderArmin GieseBernd J PichlerChristian GriesingerPublished in: ChemMedChem (2020)
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.
Keyphrases
- positron emission tomography
- pet imaging
- computed tomography
- high resolution
- pet ct
- ms ms
- small molecule
- oxidative stress
- white matter
- simultaneous determination
- binding protein
- multiple sclerosis
- human health
- real time pcr
- gene expression
- risk assessment
- loop mediated isothermal amplification
- solid phase extraction
- quantum dots
- sensitive detection