Abstract
Many neurological disorders are related to synaptic loss or pathologies. Before the boom of positrons emission tomography (PET) imaging of synapses, synaptic quantification could only be achieved in vitro on brain samples after autopsy or surgical resections. Until the mid-2010s, electron microscopy and immunohistochemical labelling of synaptic proteins were the gold-standard methods for such analyses. Over the last decade, several PET radiotracers for the synaptic vesicle 2A protein have been developed to achieve in vivo synapses visualization and quantification. Different strategies were used, namely radiolabelling with either 11C or 18F, preclinical development in rodent and non-human primates, and binding quantification with different kinetic modelling methods. This review provides an overview of these PET tracers and underlines their perspectives and limitations by focusing on radiochemical aspects, as well as preclinical proof-of-concept and the main clinical outcomes described so far.
Highlights
The synaptic vesicle glycoprotein 2A (SV2A) has been studied for three decades which were punctuated by important milestones
Developments were made with these radiotracers, andwith report the and major clinical we summarize that the preclinical developments that were made thesewe radiotracers, we outcomes by the existing achieved report the achieved major clinical outcomes by the existing positrons emission tomography (PET) radiotracers
This study revealed by ex vivo tissue distribution that the brain is one of the mice organs most exposed to radioactive doses, along with the urinary bladder wall and the liver, all the three organs receiving a resulting effective dose of 1.88·10−2 mSv·MBq−1
Summary
The synaptic vesicle glycoprotein 2A (SV2A) has been studied for three decades which were punctuated by important milestones. With previously mentioned results, Scheff et al described a positive correlation between the number of synapses in the hippocampus and the MMSE score [8] Another pertinent example consists in Molecules 2020, 25, 2303; doi:10.3390/molecules25102303 www.mdpi.com/journal/molecules. PD havepresumably a critical rolelead in presynaptic dysfunctions This in mind, the concept is that PET imaging of synaptic density could function and With presumably leadunderlying to synaptic dysfunctions. With this in mind, the underlying be achieved targeting embedded in synaptic vesicles thanks toproteins appropriate specific concept is thatbyPET imagingproteins of synaptic density could be achieved by targeting embedded in radiotracers. Report the achieved major clinical outcomes by the existing PET radiotracers
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