ESR 3 - Marion Chomet 

marion rond2

Hosted at UAntwerpen

Hosted at UAntwerpen

Objectives

Imaging the extracellular matrix process MMP-9 and uPA in the development of acquired epilepsy.

This project aims at a better understanding of the extracellular matrix in epilepsy. More specifically it focuses on developing and evaluation new possible biomarkers targeting its components. For this purpose new radiotracers will be developed targeting for example the matrix metalloproteinases or the urokinase-type plasminogen activator (uPA) and its receptor.

We aim to:

- Assess spatial and temporal changes of MMP-9 and uPA in animal models of posttraumatic epilepsyand temporal lobe epilepsy

- Investigate whether they can act as biomarkers/predictors of the long-term functional outcome

Approach

During the project, alternations in MMP-9 and uPA in rat models of acquired epilepsy will be assessed at different time points using different post-mortem techniques such as in situ/in gel zymography, immunohistochemistry, qPCR and or ELISA. The ECM proteases will also be assessed in autoradiography experiments, making use of the developed MMPs radiotracers. IN theory, peptide vectors could also be radiolabelled using NOTA or DOTA cages for SPECT and PET imaging. In a follow-up study, rats will receive an epileptogenetic insult and be subjected to in vivo PET/SPECT imaging using radiotracers that bind the ECM proteases as well as a TSPO tracer to assess inflammation. Both short-term and long-term functional outcomes of the rats will also be assessed. We will investigate whether early changes in MMP-9/uPA can predict funtional outcome.

Collaborations

- Collaboration with Iproteos: would develop MMP9 inhibitors that could be radiolabeled at Uantwerpen and evaluated in vivo

- Collaboration with Vect-Horus to improve the BBB crossing of radio ligands developed at Uantwerpen. This could be organized as a 3 months first secondment

- Other collaboration to implement new radiologists or improve the properties of the existing ones (BBB crossing and in vivo bio distribution and stability)

Participation in symposia and workshops with opportunity of networking

Page last modified on 10 apr 17 18:34