Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM

Purpose The descending raphespinal serotonin (5-HT) system contributes to neural activities required for locomotion. The presynaptic serotonin transporter (SERT) is a marker of 5-HT innervation. In this study, we explored the use of PET imaging with the SERT radioligand [C-11]AFM as a biomarker of 5-HT axon damage after spinal cord injury (SCI) in a rodent model and its translation to imaging SCI in humans. Procedures PET imaging with [C-11]AFM was performed in healthy rats under baseline and citalopram blocking conditions and a mid-thoracic transection rat model of SCI. The lumbar-to-cervical activity (L/C) ratio was calculated for the healthy and SCI animals to assess SERT binding decrease after SCI. Finally, translation of [C-11]AFM PET was attempted to explore its potential to image SCI in humans. Results Intense uptake in the brain and intact spinal cord was observed at 30-60 min post-injection of [C-11]AFM in healthy rats. About 65% of [C-11]AFM uptake in the spinal cord was blocked by citalopram. In the SCI rat model, the cervical uptake of [C-11]AFM was similar to that in healthy rats, but the lumbar uptake was dramatically reduced, resulting in about half the L/C ratio in SCI rats compared to healthy rats. In contrast, [C-11]AFM uptake in the human spinal cord showed no obvious decrease after treatment with citalopram. In the human subjects with SCI, decreases in [C-11]AFM uptake were also not obvious in the section of spinal cord caudal to the injury point. Conclusion [C-11]AFM PET imaging of SERT provides a useful preclinical method to non-invasively visualize the rodent spinal cord and detect SERT changes in SCI rodent models. However, there appears to be little detectable specific binding signal for [C-11]AFM in the human spinal cord. An SERT tracer with higher affinity and lower non-specific binding signal is needed to image the spinal cord in humans and to assess the axonal status in SCI patients.

Automated summary

The study investigated the potential use of PET imaging with SERT radioligand [C-11]AFM as a biomarker for axon damage after spinal cord injury (SCI). The results showed that the [C-11]AFM PET imaging method could effectively visualize the rodent spinal cord and detect SERT changes in SCI rodent models. However, there was limited specific binding signal for [C-11]AFM in the human spinal cord, indicating the need for a tracer with higher affinity and lower non-specific binding signal for imaging the spinal cord in humans and assessing axonal status in SCI patients.