Abstract
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 [(11)C]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 [(11)C]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 [(11)C]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 [(11)C]AFM in healthy rats. About 65% of [(11)C]AFM uptake in the spinal cord was blocked by citalopram. In the SCI rat model, the cervical uptake of [(11)C]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, [(11)C]AFM uptake in the human spinal cord showed no obvious decrease after treatment with citalopram. In the human subjects with SCI, decreases in [(11)C]AFM uptake were also not obvious in the section of spinal cord caudal to the injury point. CONCLUSION: [(11)C]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 [(11)C]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.