The Rise of Synaptic Density PET Imaging

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.

Keywords: PET radiotracers; SV2A protein; clinical outcomes; preclinical development; radiochemistry; synaptic loss.

Figure 1

Two antiepileptic drugs: Levetiracetam and Brivaracetam.

Figure 2

Individual example of [¹⁸F]UCB-H in healthy control and in mild AD patient. The white arrow heads highlight the reduced [¹⁸F]UCB-H uptake in temporal lobe areas of the mild AD patient.