Contributions
Abstract: 234
Type: Oral
Positron emission tomography, a quantitative nuclear medicine technology that uses labeled compounds recognizing specific biological targets, offers the unique opportunity to directly assess key biological mechanisms involved in MS pathophysiology, and to bridge the gap between the extensive knowledge acquired from experimental and pathological studies and in vivo imaging.
A promising application of PET is the quantification of remyelination in the brain. Several stilbene and benzothiazole derivatives have been repurposed for the dynamic imaging by PET and robust non-invasive quantification techniques were validated and recently allowed to perform longitudinal studies in vivo. They showed a great heterogeneity in individual remyelination potential during the relapsing remitting phase of the disease that was closely linked to neurological disability.
A popular target for PET microglial imaging is the TSPO macromolecular complex, which is drastically up-regulated in activated microglial cells. PET with the reference compound [11C]-PK11195 identified diffuse microglial activation in the normal appearing white matter and in the cortex of patients with a progressive form of MS. A range of improved second-generation TSPO ligands has been developed, and novel fluorinated compounds now allow to disseminate this imaging technology, opening the perspective to monitor microglial activation in longitudinal studies.
PET could also provide early markers of neurodegeneration. The central benzodiazepine receptor antagonist 11C-Flumazenil (FMZ) is an imaging marker of neuronal integrity, and has been used to quantify and regionally map the neuronal component of grey matter damage in MS, both at the group level and at the individual level. Its predictive value at the earliest stage of the disease is currently being evaluated.
The combination of PETimaging probes with MRI sequences will enable to detangle pathophysiologic mechanisms that drive disability in MS, and will contribute to the development of new therapies.
Disclosure: Lectures and boards with Teva, Biogen, Novartis, Genzyme
Research support from Genzyme and Merck-Serono
Abstract: 234
Type: Oral
Positron emission tomography, a quantitative nuclear medicine technology that uses labeled compounds recognizing specific biological targets, offers the unique opportunity to directly assess key biological mechanisms involved in MS pathophysiology, and to bridge the gap between the extensive knowledge acquired from experimental and pathological studies and in vivo imaging.
A promising application of PET is the quantification of remyelination in the brain. Several stilbene and benzothiazole derivatives have been repurposed for the dynamic imaging by PET and robust non-invasive quantification techniques were validated and recently allowed to perform longitudinal studies in vivo. They showed a great heterogeneity in individual remyelination potential during the relapsing remitting phase of the disease that was closely linked to neurological disability.
A popular target for PET microglial imaging is the TSPO macromolecular complex, which is drastically up-regulated in activated microglial cells. PET with the reference compound [11C]-PK11195 identified diffuse microglial activation in the normal appearing white matter and in the cortex of patients with a progressive form of MS. A range of improved second-generation TSPO ligands has been developed, and novel fluorinated compounds now allow to disseminate this imaging technology, opening the perspective to monitor microglial activation in longitudinal studies.
PET could also provide early markers of neurodegeneration. The central benzodiazepine receptor antagonist 11C-Flumazenil (FMZ) is an imaging marker of neuronal integrity, and has been used to quantify and regionally map the neuronal component of grey matter damage in MS, both at the group level and at the individual level. Its predictive value at the earliest stage of the disease is currently being evaluated.
The combination of PETimaging probes with MRI sequences will enable to detangle pathophysiologic mechanisms that drive disability in MS, and will contribute to the development of new therapies.
Disclosure: Lectures and boards with Teva, Biogen, Novartis, Genzyme
Research support from Genzyme and Merck-Serono