SV2A PET imaging is a non-invasive marker for the detection of spinal damages in experimental models of spinal cord injury

Traumatic spinal cord injury (SCI) is a neurological condition characterized by long-term motor and sensory neurological deficits as a consequence of an external physical impact damaging the spinal cord. Anatomical magnetic resonance imaging (MRI) is considered the gold-standard diagnostic tool to obtain structural information for the prognosis of acute SCI, however, it lacks functional objective information to assess SCI progression and recovery. In this study, we explored the use of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging to detect spinal cord lesions non-invasively following SCI. METHODS: Mice (n=7) and rats (n=8) subjected to unilateral moderate cervical (C5) contusion were euthanized 1-week post-SCI for histological and autoradiographic (³H-UCB-J) investigation of SV2A levels. Longitudinal ¹¹C-UCB-J PET/computed tomography (CT) imaging was performed in sham (n=7) and SCI rats (n=8) 1 week and 6 weeks post-SCI. Animals also underwent an ¹⁸F-FDG PET scan during the latter time point. Post-mortem tissue SV2A analysis to corroborate in vivo PET findings was performed 6 weeks post-SCI. RESULTS: A significant SV2A loss (ranging from -70.3% to -87.3%; P<0.0001) was measured at the epicenter of the impact in vitro in both mouse and rat contusion SCI models. Longitudinal ¹¹C-UCB-J PET imaging detected SV2A loss in SCI rats (- 49.0±8.1% at 1 week and -52.0±12.9% at 6 weeks post-SCI), with no change observed in sham rats. In contrast, ¹⁸F-FDG PET imaging measured only subtle hypometabolism (-17.6±14.7%). Finally, post-mortem ³H-UCB-J autoradiography correlated with the in vivo SV2A PET findings (r=0.92, P<0.0001). CONCLUSION: ¹¹C-UCB-J PET/CT imaging is a non-invasive marker for SV2A loss following SCI. Collectively, these findings indicate SV2A PET may provide an objective measure of SCI, and thus a valuable tool to evaluate novel therapeutics. Clinical assessment of SCI with SV2A PET imaging is highly recommended.