Contributions
Abstract: P1037
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Neurodegeneration is implicated in the pathogenesis of a wide range of neurologic diseases, among Multiple sclerosis (MS). In MS, diffuse white and grey matter injury are important mediators of neurodegeneration. While we are equipped with appropriate tools to image the inflammatory aspect of the disease, imaging methods to visualize diffuse brain injury are less well established.
Objectives: The aim of the present study was to investigate [18F]GE180, a novel radioligand targeting the mitochondrial translocator protein TSPO, as a PET ligand for monitoring diffuse white and grey matter injury in MS.
Methods: Diffuse demyelination and neurodegeneration were induced by cuprizone intoxication. Focal inflammatory brain lesions were established by combining cuprizone with active induction of experimental autoimmune encephalomyelitis (i.e. Cup/EAE). TSPO ligand expression was monitored by PET; immunohistochemistry was used to validate the PET imaging data. Cellular TSPO expression was investigated by immunofluorescence double labelling. Diffuse white matter injury was further investigated via 3D electron microscopy.
Results: TSPO ligand binding, determined by [18F]GE180 PET, was significantly increased in the white and grey matter of cuprizone-intoxicated mice (+51,39 ±12,48%) and Cup-EAE mice (+77,45 ±4,58%). PET-signal intensity clearly correlated with demyelination and microglia activation. TSPO was mainly expressed in activated microglia, followed by astrocytic TSPO expression. TSPO PET-signal intensity further increased, if the diffusely cuprizone-injured brain was populated by encephalitogenic T-lymphocytes. Of note, 3D electron microscopy clearly showed mitochondrial accumulation at sites of acute axonal injury. Such axonal spheroids not just stained positive for mitochondrial markers but eventually as well for TSPO.
Conclusion: [18F]GE180 PET imaging might solve the lack of a specific imaging tool for diagnosing and monitoring diffuse brain injury in MS patients. Diffuse white and grey matter injury, focal inflammatory lesions as well as axonal transport deficits might contribute to the observed increased PET signals.
Disclosure:
Anne Nack: nothing to disclose
Matthias Brendel: nothing to disclose
Carola Focke: nothing to disclose
Maximilian Deußing: nothing to disclose
Florian Eckenweber: nothing to disclose
Christian Sacher: nothing to disclose
Uta Chrzanowski: nothing to disclose
Axel Rominger: nothing to disclose
Markus Kipp: nothing to disclose
Abstract: P1037
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Neurodegeneration is implicated in the pathogenesis of a wide range of neurologic diseases, among Multiple sclerosis (MS). In MS, diffuse white and grey matter injury are important mediators of neurodegeneration. While we are equipped with appropriate tools to image the inflammatory aspect of the disease, imaging methods to visualize diffuse brain injury are less well established.
Objectives: The aim of the present study was to investigate [18F]GE180, a novel radioligand targeting the mitochondrial translocator protein TSPO, as a PET ligand for monitoring diffuse white and grey matter injury in MS.
Methods: Diffuse demyelination and neurodegeneration were induced by cuprizone intoxication. Focal inflammatory brain lesions were established by combining cuprizone with active induction of experimental autoimmune encephalomyelitis (i.e. Cup/EAE). TSPO ligand expression was monitored by PET; immunohistochemistry was used to validate the PET imaging data. Cellular TSPO expression was investigated by immunofluorescence double labelling. Diffuse white matter injury was further investigated via 3D electron microscopy.
Results: TSPO ligand binding, determined by [18F]GE180 PET, was significantly increased in the white and grey matter of cuprizone-intoxicated mice (+51,39 ±12,48%) and Cup-EAE mice (+77,45 ±4,58%). PET-signal intensity clearly correlated with demyelination and microglia activation. TSPO was mainly expressed in activated microglia, followed by astrocytic TSPO expression. TSPO PET-signal intensity further increased, if the diffusely cuprizone-injured brain was populated by encephalitogenic T-lymphocytes. Of note, 3D electron microscopy clearly showed mitochondrial accumulation at sites of acute axonal injury. Such axonal spheroids not just stained positive for mitochondrial markers but eventually as well for TSPO.
Conclusion: [18F]GE180 PET imaging might solve the lack of a specific imaging tool for diagnosing and monitoring diffuse brain injury in MS patients. Diffuse white and grey matter injury, focal inflammatory lesions as well as axonal transport deficits might contribute to the observed increased PET signals.
Disclosure:
Anne Nack: nothing to disclose
Matthias Brendel: nothing to disclose
Carola Focke: nothing to disclose
Maximilian Deußing: nothing to disclose
Florian Eckenweber: nothing to disclose
Christian Sacher: nothing to disclose
Uta Chrzanowski: nothing to disclose
Axel Rominger: nothing to disclose
Markus Kipp: nothing to disclose