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

Area of Science:

• Neuroscience
• Radiology
• Biomarker Discovery

Background:

• Traumatic spinal cord injury (SCI) causes significant motor and sensory deficits.
• Anatomic MRI lacks sensitivity for functional synaptic changes crucial for prognosis.
• Noninvasive imaging of synaptic alterations is needed for SCI assessment and therapeutic evaluation.

Purpose of the Study:

• To evaluate ¹⁸F-SynVesT-1 PET imaging for noninvasively measuring synaptic vesicle glycoprotein 2A (SV2A) loss in a rat SCI model.
• To determine if SV2A PET can detect SCI severity-dependent synaptic loss.
• To validate in vivo PET findings with ex vivo methods.

Main Methods:

• Rats underwent graded contusion SCI (100, 250, 400 kDyn) or sham surgery.
• Longitudinal ¹⁸F-SynVesT-1 PET/CT and structural MRI were performed at 1 and 6 weeks post-injury.
• Postmortem SV2A immunostaining and autoradiography were used for validation.

Main Results:

• Structural MRI showed lesion volumes proportional to SCI severity.
• ¹⁸F-SynVesT-1 PET detected significant SV2A reduction at the injury epicenter, proportional to injury severity (P < 0.0001 at 1 wk).
• SV2A loss was sustained at 6 weeks and strongly correlated with ex vivo validation.

Conclusions:

• ¹⁸F-SynVesT-1 PET is a sensitive, noninvasive method to measure SV2A loss in SCI.
• SV2A PET can discriminate between different injury severities.
• SV2A PET serves as an objective early biomarker for SCI severity and progression, valuable for therapy evaluation.