Beyond the brain: Imaging spinal cord injury with PET and [11C]AFM

330 Objectives: Spinal cord injury (SCI) produces neurological deficits by severing nerve fibers. Serotonergic axons descend from the raphe to the spinal cord and contribute to motor tone and locomotion. In rodents, the raphespinal pathway is sensitive to axonal growth promoting interventions and is predictive of behavior outcomes. We seek an imaging method to monitor axonal regrowth after SCI, using PET and [11C]AFM, a serotonin transporter (SERT) ligand. Methods: Healthy rats and rats with midthoracic cord contusion were each scanned twice on the HRRT wtih [11C]AFM: one control and one blocking scan after citalopram. Two regions of interest were assessed in the spinal cord: a cervical zone rostral and a lumbar zone caudal to the injury site. The lumbar to cervical activity ratio between 30-60 min was used as a measure of descending axon density below the level of injury. Results: Uptake was distinctly higher within the spinal cord compared to surrounding tissues. In healthy rats, [11C]AFM activity was 0.22 and 0.21% ID/mL in the lumbar and cervical zones (ratio of 1.06). After citalopram these values were reduced by ~ 80%, indicating that [11C]AFM binding was specific to SERT in the spinal cord. In the spinal injured rats the lumbar singnal was significantly reduced relative to the cervical signal, with a lumbar/cervical ratio of 0.41. The reduced [11C]AFM signal in the lumbar cord of injured rats correlated well with post-mortem histological analysis of 5-HT and SERT signals. Conclusions: Imaging of SERT in the spinal cord provides a promising biomarker for initial loss of axonal density and axonal regeneration after SCI. Once validated in humans this method will be a valuable tool for assessing SCI and monitoring clinical outcomes in SCI therapeutic trials.