SV2A PET Imaging Detects Severity-Dependent Synaptic Changes After Experimental Traumatic Spinal Cord Injury

Traumatic spinal cord injury (SCI) is a serious neurologic disorder that can result in long-term motor and sensory impairments after external damage to the spinal cord. Although anatomic MRI offers essential structural information, it falls short in capturing functional alterations, particularly synaptic changes, which are crucial for accurate prognosis and evaluating therapeutic outcomes. Here, we used ¹⁸F-SynVesT-1 PET imaging to measure noninvasively synaptic vesicle glycoprotein 2A (SV2A) loss in a rat model of SCI to determine whether SV2A PET is capable of detecting SCI severity-dependent synaptic loss. <b>Methods:</b> Rats were subjected to laminectomy (sham, <i>n</i> = 10) or unilateral cervical (C5) contusion injury with graded severity (100 kDyn, <i>n</i> = 10; 250 kDyn, <i>n</i> = 10; and 400 kDyn, <i>n</i> = 10). Longitudinal ¹⁸F-SynVesT-1 PET/CT imaging and structural MRI were performed at 1 and 6 wk after SCI. SV2A immunostaining and ³H-SynVesT-1 autoradiography were conducted to validate in vivo PET findings. <b>Results:</b> Structural MRI revealed lesion volumes proportional to contusion severity in SCI rats at both 1 wk (<i>P</i> < 0.0001) and 6 wk (<i>P</i> = 0.0190) after SCI, with overall lesion volume decreasing over time. ¹⁸F-SynVesT-1 PET imaging detected a significant reduction in SV2A at the injury epicenter proportional to injury severity: -37.5 ± 5.5% (100 kDyn), -39.2 ± 3.7% (250 kDyn), and -41.9 ± 3.5% (400 kDyn) at 1 wk after SCI compared with sham controls (<i>P</i> < 0.0001). At 6 wk after SCI, the SV2A loss remained sustained, showing no progression over time. Postmortem immunofluorescence and autoradiography confirmed SV2A loss to be proportional to injury severity and strongly correlated with the in vivo PET. <b>Conclusion:</b> ¹⁸F-SynVesT-1 PET imaging provides a sensitive, noninvasive measure of SV2A loss after SCI and can discriminate between different levels of injury severity. Together, these findings support SV2A PET as an early objective biomarker for SCI severity and progression, offering a valuable tool for evaluating new therapies and further encouraging clinical application of SV2A PET for SCI assessment.