Feasibility of imaging synaptic density in the human spinal cord using [11C]UCB-J PET

Abstract

Purpose Neuronal damage and synapse loss in the spinal cord (SC) have been implicated in spinal cord injury (SCI) and neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS). Current standards of diagnosis for SCI include CT or MRI imaging to evaluate injury severity. The current study explores the use of PET imaging with [11C]UCB-J, which targets the synaptic vesicle protein 2A (SV2A), in the human spinal cord, as a way to visualize synaptic density and integrity in vivo. Results First, simulations of baseline and blocking [11C]UCB-J HRRT scans were performed, based on SC dimensions and SV2A distribution to predict VT, VND, and VS values. Next, human baseline and blocking [11C]UCB-J HRRT images were used to estimate these values in the cervical SC (cSC). Simulation results had excellent agreement with observed values of VT, VND, and VS from the real human data, with baseline VT, VND, and VS of 3.07, 2.15, and 0.92 mL/cm3, respectively, with a BPND of 0.43. Lastly, we explored full SC imaging with whole-body images. Using automated SC regions of interest (ROIs) for the full SC, cSC, and thoracic SC (tSC), the distribution volume ratio (DVR) was estimated using the brain gray matter as a reference region to evaluate SC SV2A density relative to the brain. In full body imaging, DVR values of full SC, cSC, and tSC were 0.115, 0.145, and 0.112, respectively. Therefore, measured [11C]UCB-J uptake, and thus SV2A density, is much lower in the SC than in the brain. Conclusions The results presented here provide evidence for the feasibility of SV2A PET imaging in the human SC, however, specific binding of [11C]UCB-J is low. Ongoing and future work include further classification of SV2A distribution in the SC as well as exploring higher-affinity PET radioligands for SC imaging.

GMP-compliant automated radiosynthesis of [18F] SynVesT-1 for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)

“…SV2A is widely distributed in the nervous system, in virtually all neurons. (Maria Portela-Gomes et al, 2000), including in the brain and the spinal cord (Samantha Rossano et al, 2022). Given the limitations and the limited resolution of whole-body PET imaging, the as-prepared [ 18 F] SynVesT-1 meets the requirements for human injection and conduct whole body in vivo imaging scans to assess the distribution of synaptic density in various locations throughout the body.…”

Bringing synapses into focus: Recent advances in synaptic imaging and mass-spectrometry for studying synaptopathy

“…This exciting work revealed region-specific synaptic change that associates with cognitive change and genotype. As the utility of this approach widens, there is interesting recent evidence that synaptic PET imaging in the spinal cord is possible ( Rossano et al, 2022 ), which will be important for diseases like ALS as well as understanding spinal cord injury and monitoring regeneration.…”

The Pons as an Optimal Background Reference Region for Spinal 18F-FET PET/MRI Evaluation

“…By detecting metabolic activity and tracer uptake, which traditional imaging techniques, such as CT or MRI, could not illustrate, PET enables the characterization of various spinal conditions. Currently, PET has been utilized as a tool for the diagnosis, monitoring of treatment response, and even guiding surgical interventions for diseases such as tumors [2][3], spondylosis [4][5], amyotrophic lateral sclerosis [6-8], spinal cord injuries [9], multiple sclerosis [10] and so on.…”