Summary: Researchers developed a new PET tracer capable of measuring synapse loss after spinal cord injury, offering insights into both spinal and brain changes. In rat models, the tracer revealed significant synaptic reductions at the injury site and in distant brain regions, highlighting how widespread the effects of injury can be.
Compared with traditional imaging, this approach provides unique molecular-level detail, making it a valuable tool for assessing therapeutic outcomes. The work opens the door to more precise diagnosis and personalized treatment strategies for spinal cord injury patients.
Key Facts
- Tracer Innovation: [18F]SynVesT-1 PET identifies synapse loss after spinal cord injury.
- Quantitative Findings: 52–58% reduction in tracer uptake at injury sites, with additional loss in brain regions.
- Clinical Potential: Provides an objective, non-invasive metric for monitoring recovery and testing therapies.
Source: SNMMI
A new PET tracer can provide insights into how spinal cord injuries affect not only the spinal cord, but also the brain, according to new research published in The Journal of Nuclear Medicine.
By identifying synapse loss, the PET approach provides molecularly unique and complementary information to other structural imaging methods, offering a promising objective metric to evaluate novel therapeutics for spinal cord injuries.
According to the National Spinal Cord Injury Statistical Center, the annual incidence of traumatic spinal cord injury is about 54 cases per one million people, and approximately 308,600 people in the United States live with a spinal cord injury.
Clinical outcomes vary based on injury severity and location, potentially leading to partial or complete loss of sensory or motor function below the injury level. Current clinical spinal cord injury diagnosis relies on anatomic techniques such as x-ray and CT, which assess spinal integrity but provide limited physiologic and pathologic information.
“There is an urgent need for a quantitative and non-invasive imaging method for neural network changes after spinal cord injury,” said Jason Cai, PhD, associate professor of radiology and biomedical imaging and of pharmacology at Yale School of Medicine in New Haven, Connecticut.
“By offering a non-invasive quantitative method to visualize and quantify synapse loss in the whole central nervous system, SV2A PET could become an essential tool for evaluating and monitoring the progression of spinal cord injury or predict recovery.”
Researchers used the newly developed 18F-labeled SV2A radiotracer, [18F]SynVesT-1, to assess changes in synaptic density in a rat model of T7 contusion. Nine rats with T7 spinal cord injuries and seven sham controls were imaged with [18F]SynVesT-1 PET on day one and on days nine through 11 after injury. Imaging findings of the injury site and of the brain were compared with ex vivo diffusion tensor imaging (DTI) and molecular biologic analyses.
[18F]SynVesT-1 PET effectively identified synapse loss in the contusion SCI rat model. Uptake at the spinal cord injury epicenter was found to be reduced by 58 percent and 52 percent on day one and days nine through 11 after injury, respectively, compared with the sham control rats.
The uptake of 18F-SynVesT-1 in the amygdala and cerebellum was also lower in spinal cord injury rats, and ex vivo DTI analysis revealed fiber damage in the internal capsule and somatosensory cortex.
“Our work has potential to revolutionize the way spinal cord injury is diagnosed and monitored in the clinic, noted Cai. SV2A PET could be used to evaluate the effects of new treatments objectively and quantitatively, supporting more precise and personalized therapeutic strategies for patients with spinal cord injuries.”
COI Statement
Fahmeed Hyder is the founder of Innovacyclics, LLC. Zhengxin Cai is a cofounder of Synvest Imaging Inc. Richard Carson, Yiyun Huang, and Zhengxin Cai are inventors on PCT/US2018/018388, which covers the SV2A PET tracer used in this study.
About this neuroimaging and SCI research news
Author: Susan Martonik
Source: SNMMI
Contact: Susan Martonik – SNMMI
Image: The image is credited to Neuroscience News
Original Research: Open access.
“[18F]SynVesT-1 PET Detects SV2A Changes in the Spinal Cord and Brain of Rats with Spinal Cord Injury” by Jason Cai et al. Journal of Nuclear Medicine
Abstract
[18F]SynVesT-1 PET Detects SV2A Changes in the Spinal Cord and Brain of Rats with Spinal Cord Injury
Traumatic spinal cord injury (SCI) is a devastating neurologic condition lacking effective prognostic and treatment methods. PET imaging of synaptic vesicle glycoprotein 2A (SV2A) has been used in measuring synapse changes. We explore the feasibility of using [18F]SynVesT-1 PET to detect the synaptic changes in a rat model of SCI.
Methods: [18F]SynVesT-1 PET scans were performed on rats with T7 moderate contusion injury (n = 9) and sham controls (n = 7) on day 1 and days 9–11 after injury. The simplified reference region method 2 was used to compute the distribution volume ratios (DVRs) for the spinal cord (SC) and the brain, with the cervical cord and brain stem as the reference region, respectively.
The averaged SUV ratio 30–60 min after injection was calculated as an alternative outcome measure. Diffusion tensor imaging (DTI) was used to evaluate axonal changes on post mortem SCs. Western blotting, immunohistochemical staining, and immunofluorescence staining were used to confirm the imaging results.
Results: [18F]SynVesT-1 showed the highest uptake in the cervical SC. Notably, the DVR at the injury epicenter in SCI rats showed a 61% decrease on day 1 and a 53% decrease on days 9–11, compared with sham controls. The changes in SUV ratio 30–60 min after injection were consistent with the changes in DVR.
The fiber damage in the epicenter was identified by DTI, and the loss of SV2A was confirmed by immunohistochemical staining and Western blotting. Further, the amygdala, limbic insular cortex, and cerebellum were found to be significantly affected by the SCI on day 1 by PET. The DTI analysis revealed fiber damage in the internal capsule and somatosensory cortex.
Conclusion: [18F]SynVesT-1 PET effectively identified synapse loss in the contusion SCI rat model. The quantification of synaptic density through SV2A PET presents a promising objective metric for evaluating novel therapeutics for SCI.
