Monitoring spinal cord injury and treatment outcome with PET imaging

Objectives We have demonstrated that PET imaging of serotonin transporter (SERT) with the novel tracer [¹¹C]AFM is effective in assessing spinal cord injury (SCI). Here we report our findings of spinal SERT imaging as a sensitive biomarker to monitor axon regrowth in response to therapy in a rodent model of chronic SCI.

Methods Dynamic PET scans were performed on the HRRT in 4 groups of animals: healthy rats, rats injured with thoracic spinal contusion and untreated for 3 months, injured rats treated for 12 weeks with the control IgG protein, or the Nogo receptor fragment NgR(310)-ecto-Fc protein, which promotes axon regrowth. Volumes of interest (VOI) were defined: a cervical zone rostral to the injury site and a lumbar zone caudal to the injury level. Activity uptake was measured in these two VOIs. The lumbar to cervical activity (LUM/CER) ratio was then used as a measure of descending axon density below the level of injury.

Results In healthy rats (n=8), the LUM/CER [¹¹C]AFM uptake ratio was 1.00±0.20, indicating similar SERT density throughout the cord. In chronically injured rats, cervical [¹¹C]AFM uptake was similar to that in uninjured animals, but lumbar uptake was dramatically reduced, resulting in a LUM/CER ratio of 0.23±0.03 (n=23). In injured rats (n=21) treated with NgR(310)-ecto-Fc protein, LUM/CER ratio increased to about twice (0.38±0.06) of that in untreated animals, indicating a significant regrowth of 5-HT axon in the treated group (p<0.05). In contrast, injured rats treated with IgG protein (n=21) showed no increase in LUM/CER signal (ratio of 0.22±0.05). These imaging results matched closely those from post-mortem immunohistological analysis of 5-HT and SERT activities, as well as behavior measurements.

Conclusions PET imaging of spinal SERT appears to be a promising biomarker for axon loss after SCI and re-growth in response to therapy. When successfully translated to humans, this non-invasive method will be a valuable tool for monitoring and correlating clinical outcomes in SCI therapy trials