Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy

Abstract

Purpose The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. Procedures Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [18F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. Results Control rats presented a significant increase in [18F]UCB-H binding at the last two scans, compared with the first ones (p < 0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p < 0.028). Furthermore, the quantification of the SV2A expression in vivo with the [18F]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both. Conclusions Even if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [18F]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease.

The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

“…Additionally, this [ 18 F]UCB-H clinical study [25] suggested a widespread synaptic decline in AD patients across the neocortex and in some subcortical nuclei, including the basal forebrain, which was confirmed in a comparable but larger cohort of AD patients using [ 11 C]UCB-J [42]. These and other data [43] have demonstrated the potential of the [ 18 F] UCB-H radioligand.…”

Structural and Functional Neuroplasticity Following Bilateral Vestibular Loss: A Longitudinal [18F]-UCB-H/[18F]-FDG Dual Tracer Rat Study

“…Recently, it was shown that the [ 11 C]-UCB-J signal was not affected by short-term changes in neuronal activity during an activation task 37,38 . On the other hand, short-term dynamics in [ 18 F]-UCB-H binding were depicted in a temporal lobe epilepsy model, which depended on the disease stage 39 . In a mouse model of Alzheimer disease, therapeutic effects of a disease-modifying drug could be visualized and quanti ed by [ 18 F]-UCB-H-PET imaging 40 .…”

TSPO PET upregulation predicts epileptic phenotype at disease onset independently from chronic TSPO expression in a rat model of temporal lobe epilepsy

“…In the present study, we have demonstrated a declined hippocampal synaptic density during chronic epilepsy, however, it was mainly restricted to the CA1 layer and not associated with seizure frequency. While such focal reduction might be difficult to detect in vivo given the spatial resolution of microPET cameras (range of 0.8–1.5 mm), the potential application of SV2A PET imaging as a non-invasive marker for epilepsy is supported by recent work demonstrating its applicability in rodents ( Bertoglio et al, 2019b , Thomsen et al, 2020 ), evidence of reduced synaptic density in KASE rats during the progression of epilepsy ( Serrano et al, 2020 ) and further corroborated by the observation that SV2A PET can detect the epileptogenic focus in patients with refractory TLE ( Finnema et al, 2016 , Finnema et al, 2020 ).…”