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. Methods: Mice (n = 7) and rats (n = 8) subjected to unilateral moderate cervical (C5) contusion were euthanized 1 wk after SCI for histologic and autoradiographic (³H-labeled (4R)-1-[(3-methylpyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one [UCB-J]) investigation of SV2A levels. Longitudinal ¹¹C-UCB-J PET/CT imaging was performed in sham (n = 7) and SCI rats (n = 8) 1 wk and 6 wk after SCI. Animals also underwent an ¹⁸F-FDG PET scan during the latter time point. Postmortem tissue SV2A analysis to corroborate in vivo PET findings was performed 6 wk after 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 wk and –52.0% ± 12.9% at 6 wk after SCI), with no change observed in sham rats. In contrast, ¹⁸F-FDG PET imaging measured only subtle hypometabolism (–17.6% ± 14.7%). Finally, postmortem 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 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.

创伤性脊髓损伤 (SCI) 是一种神经系统疾病，其特征是由于外部物理冲击损伤脊髓而导致长期运动和感觉神经功能障碍。解剖 MRI 被认为是获得急性 SCI 预后结构信息的金标准诊断工具；然而，它缺乏评估 SCI 进展和恢复的功能性客观信息。在这项研究中，我们探索了使用突触小泡糖蛋白 2A (SV2A) PET 成像在 SCI 后无创检测脊髓损伤。方法：单侧颈椎中度（C5）挫伤后1周处死小鼠（n =7）和大鼠（n =8）进行组织学和放射自显影（ ^3H标记（4R )-1-[(3-methylpyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one [UCB-J]) 对 SV2A 水平的研究。在 SCI 后 1 周和 6 周，在假手术 ( n = 7) 和 SCI 大鼠 ( n = 8) 中进行纵向¹¹ C-UCB-J PET/CT 成像。在后一个时间点，动物还接受了^{18 F-FDG PET 扫描。}SCI 后 6 周进行尸检组织 SV2A 分析以证实体内 PET 发现。结果：在小鼠和大鼠挫伤 SCI 模型的体外冲击中心测量到显着的 SV2A 损失（范围从 –70.3% 到 –87.3%；P < 0.0001）。纵向¹¹C-UCB-J PET 成像检测到 SCI 大鼠的 SV2A 丢失（1 周时为–49.0% ± 8.1%，SCI 后 6 周时为–52.0% ± 12.9%），在假大鼠中未观察到变化。相比之下，¹⁸ F-FDG PET 成像仅测量到轻微的低代谢 (–17.6% ± 14.7%)。最后，尸检³ H-UCB-J 放射自显影与体内 SV2A PET 结果相关（r = 0.92，P < 0.0001）。结论： ¹¹ C-UCB-J PET/CT 成像是 SCI 后 SV2A 丢失的无创标志物。总的来说，这些发现表明 SV2A PET 可以提供 SCI 的客观测量，因此代表了评估新疗法的有价值的工具。强烈建议使用 SV2A PET 成像对 SCI 进行临床评估。