Huntington's Disease: A Review of the Known PET Imaging Biomarkers and Targeting Radiotracers

Molecules. 2020 Jan 23;25(3):482. doi: 10.3390/molecules25030482.


Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG expansion mutation in the huntingtin gene. As a result, intranuclear inclusions of mutant huntingtin protein are formed, which damage striatal medium spiny neurons (MSNs). A review of Positron Emission Tomography (PET) studies relating to HD was performed, including clinical and preclinical data. PET is a powerful tool for visualisation of the HD pathology by non-invasive imaging of specific radiopharmaceuticals, which provide a detailed molecular snapshot of complex mechanistic pathways within the brain. Nowadays, radiochemists are equipped with an impressive arsenal of radioligands to accurately recognise particular receptors of interest. These include key biomarkers of HD: adenosine, cannabinoid, dopaminergic and glutamateric receptors, microglial activation, phosphodiesterase 10 A and synaptic vesicle proteins. This review aims to provide a radiochemical picture of the recent developments in the field of HD PET, with significant attention devoted to radiosynthetic routes towards the tracers relevant to this disease.

Keywords: Huntington’s disease; Positron Emission Tomography; [11C]raclopride; [18F]MNI-659; carbon-11; fluorine-18; mutant huntingtin; radiochemistry; radiopharmaceuticals.

Publication types

  • Review

MeSH terms

  • Biomarkers / metabolism*
  • Brain / diagnostic imaging*
  • Brain / pathology
  • Cannabinoid Receptor Agonists / metabolism
  • Carbon Radioisotopes / chemistry
  • Dopamine Antagonists / chemical synthesis
  • Dopamine Antagonists / chemistry
  • Dopamine Antagonists / metabolism
  • Excitatory Amino Acid Antagonists / chemical synthesis
  • Excitatory Amino Acid Antagonists / chemistry
  • Excitatory Amino Acid Antagonists / metabolism
  • Fluorine Radioisotopes / chemistry
  • GABA Antagonists / chemical synthesis
  • GABA Antagonists / chemistry
  • GABA Antagonists / metabolism
  • Humans
  • Huntington Disease / diagnostic imaging*
  • Huntington Disease / pathology
  • Microglia / metabolism
  • Phosphodiesterase Inhibitors / chemical synthesis
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / metabolism
  • Positron-Emission Tomography*
  • Purinergic P1 Receptor Antagonists / chemical synthesis
  • Purinergic P1 Receptor Antagonists / chemistry
  • Purinergic P1 Receptor Antagonists / metabolism
  • Radiopharmaceuticals* / chemistry


  • Biomarkers
  • Cannabinoid Receptor Agonists
  • Carbon Radioisotopes
  • Dopamine Antagonists
  • Excitatory Amino Acid Antagonists
  • Fluorine Radioisotopes
  • GABA Antagonists
  • Phosphodiesterase Inhibitors
  • Purinergic P1 Receptor Antagonists
  • Radiopharmaceuticals