SV2A PET Imaging Is a Noninvasive Marker for the Detection of Spinal Damage in Experimental Models of Spinal Cord Injury

Traumatic spinal cord injury (SCI) is a neurologic condition characterized by long-term motor and sensory neurologic deficits as a consequence of an external physical impact damaging the spinal cord. Anatomic 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) PET imaging to detect spinal cord lesions noninvasively after SCI. Mice ( = 7) and rats ( = 8) subjected to unilateral moderate cervical (C5) contusion were euthanized 1 wk after SCI for histologic and autoradiographic ( H-labeled (4 )-1-[(3-methylpyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one [UCB-J]) investigation of SV2A levels. Longitudinal C-UCB-J PET/CT imaging was performed in sham ( = 7) and SCI rats ( = 8) 1 wk and 6 wk after SCI. Animals also underwent an F-FDG PET scan during the latter time point. Postmortem tissue SV2A analysis to corroborate in vivo PET findings was performed 6 wk after SCI. A significant SV2A loss (ranging from -70.3% to -87.3%; < 0.0001) was measured at the epicenter of the impact in vitro in both mouse and rat contusion SCI models. Longitudinal C-UCB-J PET imaging detected SV2A loss in SCI rats (-49.0% ± 8.1% at 1 wk and -52.0% ± 12.9% at 6 wk after SCI), with no change observed in sham rats. In contrast, F-FDG PET imaging measured only subtle hypometabolism (-17.6% ± 14.7%). Finally, postmortem H-UCB-J autoradiography correlated with the in vivo SV2A PET findings ( = 0.92, < 0.0001). C-UCB-J PET/CT imaging is a noninvasive marker for SV2A loss after SCI. Collectively, these findings indicate that SV2A PET may provide an objective measure of SCI and thus represent a valuable tool to evaluate novel therapeutics. Clinical assessment of SCI with SV2A PET imaging is highly recommended.