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

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.

First, simulations of baseline and blocking [¹¹C]UCB-J HRRT scans were performed, based on SC dimensions and SV2A distribution to predict V_T, V_ND, and V_S 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 V_T, V_ND, and V_S from the real human data, with baseline V_T, V_ND, and V_S of 3.07, 2.15, and 0.92 mL/cm³, respectively, with a BP_ND 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.

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.