Imaging traumatic brain injuries in mice with potassium channel PET tracer [ 18 F]3F4AP
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Objective
Traumatic brain injury (TBI) can lead to secondary injury, including axon and myelin damage, which contributes to long-term neurological deficits. The PET tracer [ 18 F]3F4AP, a fluorinated derivative of the FDA-approved drug 4-aminopyridine, selectively binds to voltage-gated potassium (K V ) channels, offering a novel approach to assess TBI-related node of Ranvier disruption and demyelination. This study evaluates [ 18 F]3F4AP PET in penetrating and non-penetrating TBI models.
Methods
Either controlled cortical impact (CCI, penetrating) or concussive (non-penetrating) TBI models were used to induce TBI in mice. Dynamic PET imaging with [ 18 F]3F4AP was performed at time points of 0, 3, 7, 14, and/or 31 days post-injury (dpi), with quantitative analyses comparing tracer uptake in injured versus control regions. Luxol fast blue (LFB) staining was conducted to evaluate histological myelin loss.
Results
In the CCI model, [ 18 F]3F4AP PET imaging demonstrated a 34% increase in tracer uptake at the injury site at 7 dpi, correlating with histological evidence of demyelination. Tracer uptake gradually declined over time, reflecting potential remyelination. The concussive TBI model showed a smaller and more diffuse increase in uptake at 7 dpi compared to CCI.
Conclusion
[ 18 F]3F4AP PET imaging effectively detects demyelination following TBI, with very high sensitivity in penetrating injuries. These findings highlight the potential of [ 18 F]3F4AP as a valuable imaging biomarker for assessing TBI progression and/or therapeutic response. Further studies are warranted to explore its clinical applicability and comparison with other imaging modalities.
