Abstract
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.
Highlights
The purpose of this review is to provide a radiochemistry focused summary of the recent advancements in Positron Emission Tomography (PET) imaging of a rare genetic condition, Huntington’s disease (HD)
The authors’ intention is to highlight the importance of radiochemistry and design of novel and highly specific radioligands for PET imaging, which will further our understanding of the changes orchestrated by mutant huntingtin and may eventually lead to the invention of disease-modifying treatments
This review summarises the key biochemical targets within the central nervous system which could be relevant for HD and the corresponding PET radioligands, along with their radiosynthetic routes
Summary
The purpose of this review is to provide a radiochemistry focused summary of the recent advancements in Positron Emission Tomography (PET) imaging of a rare genetic condition, Huntington’s disease (HD). The prevalence of HD is 5 to 10 cases per 100,000 people worldwide [1] It progresses with fatal and devastating psychiatric, cognitive and motor impairments, caused by mutant huntingtin (mHTT) protein expression. A suitable PET tracer and its radiosynthesis are provided, together with the most important PET data, both clinical and preclinical, if available. The authors’ intention is to highlight the importance of radiochemistry and design of novel and highly specific radioligands for PET imaging, which will further our understanding of the changes orchestrated by mutant huntingtin and may eventually lead to the invention of disease-modifying treatments.
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