Longitudinal in vivo evaluation of brain synaptic density with [18F]UCB-H through the different phases in the kainic acid rat model of temporal lobe epilepsy.

Epilepsy is one of the most common neurological disorders, affecting around 65 million people worldwide. Since some of the most efficient antiepileptic drugs target the SV2A protein, different radiotracers have been developed to detect and monitor its variations in the epileptic disease, being proposed as synaptic density markers. Our research focus on the longitudinal SV2A quantification in different brain regions of the kainic acid rat model of temporal lobe epilepsy, using the [18F]UCB-H radiotracer. Furthermore, we evaluated the relationship between these variations and three EEG parameters: the number of electrographic seizures per week and their mean and total duration. In addition, we have confirmed the correct development of our model and the [18F]UCB-H results by means of the magnetic resonance imaging (performed in parallel to [18F]UCB-H scans), the electroencephalography technique (during one week after PET imaging), and the SV2A immunofluorescence (performed at the end of the electroencephalography). Our quantitative analyses evidence a progressive decrease in the synaptic density in all the brain regions assessed, showcasing the ability of the [18F]UCB-H to detect and monitor variations in the synaptic density through the epileptic disease. Furthermore, the epileptic animals which suffered the highest number of electrographic seizures were those presenting the lowest brain metabolism, but the lowest SV2A decrease. Hence, these first-in-class results highlight not only the utility of [18F]UCB-H as a diagnosis, monitoring and pharmacodynamics/response biomarker, but also they suggest that the [18F]UCB-H uptake reflects the synaptic function in the epileptic group, which suppose a big step understanding the epilepsy.