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Alpha-Synuclein PET Tracer Development-An Overview about Current Efforts.

Špela Korat1, Natasha Shalina Rajani Bidesi2, Federica Bonanno3

  • 1Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universeit Amsterdam, De Boelelaan 1085c, 1081 HV Amsterdam, The Netherlands.

Pharmaceuticals (Basel, Switzerland)
|September 28, 2021
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Summary

Developing novel positron emission tomography (PET) tracers for alpha-synuclein (α-syn) is crucial for diagnosing and monitoring neurodegenerative diseases like Parkinson's. Current challenges include low abundance, intracellular localization, and selectivity issues, hindering non-invasive α-syn detection.

Keywords:
alpha-synucleinimagingpositron emission tomographysynucleinopathies

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Area of Science:

  • Neuroscience
  • Radiochemistry
  • Molecular Imaging

Background:

  • Neurodegenerative diseases like Parkinson's are characterized by alpha-synuclein (α-syn) inclusions, detectable only postmortem.
  • Non-invasive detection of α-syn is vital for understanding disease progression and enabling early diagnosis.
  • Positron emission tomography (PET) offers non-invasive in vivo imaging, but requires specific tracers for target quantification.

Purpose of the Study:

  • To provide a comprehensive review of current research and challenges in developing selective α-syn PET tracers.
  • To highlight the need for high-affinity ligands due to low α-syn abundance in the brain.
  • To address difficulties in targeting intracellular α-syn and ensuring selectivity over similar proteins.

Main Methods:

  • Review of existing literature on α-syn PET tracer development.
  • Analysis of challenges including ligand affinity, accessibility, and selectivity.
  • Discussion of strategies to overcome hurdles in tracer design.

Main Results:

  • The development of α-syn PET tracers faces significant challenges.
  • High ligand affinity is required due to low α-syn abundance.
  • Selectivity over amyloid-beta and tau is critical, as is overcoming intracellular localization.

Conclusions:

  • Novel α-syn PET tracers are essential for advancing the diagnosis and treatment monitoring of α-synucleinopathies.
  • Overcoming current challenges is key to successful tracer development.
  • Further research is needed to design effective and selective α-syn PET imaging agents.