Journal of Isotopes (Aug 2023)
Novel Brain Synaptic Density Nuclide Molecular Probe 18F-SynVesT-1 Radiolabeling, Quality Control and Imaging Analysis
Abstract
Neural synapses were the fundamental sites of interneuronal connections and the structural basis for information transmission in brain networks, and alterations in synapse density were closely related to a variety of nervous system disorders. Therefore, in vivo visual evaluation and quantitative measurement of synaptic density have broad clinical application prospects in the diagnosis, therapeutic monitoring, and potential mechanism research for neurological and psychiatric diseases. Previous research demonstrated that synaptic vesicle protein 2A (SV2A) located in neurons' presynaptic membrane of the brain gray matter could effectively reflect the synaptic density of the central nervous system, while also being closely related to neuronal excitatory changes, the epileptogenic network formation progress and epilepsy drug resistance. It was envisaged that novel nuclide molecular probes targeting SV2A will be developed and utilized to measure alterations in synaptic density in a variety of neurological and psychiatric disorders. This study intended to perform radioactive labeling and quality control for the first time on a high-specificity targeted synaptic density PET imaging agent, 18F-SynVesT-1. The GE Tracerlab FXFN module was used for agent automated agent synthesis while the physical and chemical properties, stability, specific activity, bacterial endotoxin, and other elements of the product solution were analyzed for agent quality control. And finally, the 18F-SynVesT-1 PET imaging performance verification was verified using animal models of epilepsy. The results of this study showed that the GE TRACERLAB FXFN module could achieve an efficient synthesis of 18F-SynVesT-1 with an uncalibrated yield of (11.4±2.6)%, and the product solution synthesized could meet the standard requirements of injection safety and routine clinical command for invasively disease evaluation. This study indicated that the objective product 18F-SynVesT-1 synthesized had good quality control performance and that 18F-SynVesT-1 PET/CT could be used for brain synaptic change assessment in vivo imaging, density quantitative evaluation, detection, and analysis of epileptogenic abnormalities.
Keywords