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2010-05-19 - Colloque/Présentation - poster - Anglais - 1 page(s)

Sclavons Coralie, Burtea Carmen , Laurent Sophie , Toubeau Gérard, Vander Elst Luce , Muller Robert , "MRI targeting of apoptotic cells in injured areas of brain in a mouse model of Parkinson's disease" in Contrast-enhanced biomedical imaging, 12th Bi-Annual Conference on Contrast Agents and Multimodal Molecular Imaging, Mons, Belgique, 2010

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Neuropathologie (DI332C), Chimie organique (DI1313), Chimie des colloïdes (DI1329), Imagerie médicale, radiologie, tomographie (DI3243)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Histologie (M118)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)

Abstract(s) :

(Anglais) Purpose Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a massive loss of dopaminergic neurons (DN) located in the basal ganglia, both by apoptosis and by neuro-inflammation. In order to facilitate early diagnosis of this disease, a peptide specific to apoptotic cells identified by phage display [1] was grafted to a magnetic reporter and used to image injured areas in PD by MRI. Materials and method The peptide (PPS), specific to phosphatidylserine exposed on the outer leaflet of cell membrane during apoptosis, has been conjugated to ultra small particles of iron oxide (USPIO-PPS). The affinity of USPIO-PPS for apoptotic cells was tested. DN cultures were incubated with USPIO-PPS and the cell samples were examined by MRI, R2 relaxation rate measurement and Fe concentration assessment. Apoptosis was induced by MPP+ (1-methyl-4- phenylpyridinium), which on a molecular level mimics PD in DN culture. USPIO-PPS was also injected to MPTP-treated mice (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine, which is a neurotoxin inducing PD). Mice were then analyzed by MRI on a Bruker AVANCE-200 spectrometer working at 4.7T and equipped with a vertical magnet and a micro-imaging system. Results The interaction of USPIO-PPS with MPP+-treated DN cultures was confirmed by MRI, R2 and iron concentration measurements made on cell samples. The MR images acquired on MPTP-treated mice injected with USPIO-PPS showed that the targeted areas in brain correspond to the injured region in Parkinsonian mice; dopaminergic neurons were immuno- stained after MRI sessions with anti-tyrosine hydroxylase antibody. Conclusion Affected areas in PD can be imaged in MPTP-treated mice by targeting apoptotic cells with USPIO vectorized by a phosphatidylserine-specific peptide. References (1) Burtea C, Laurent S, Lancelot E, Ballet S, Murariu O, Rousseaux O, Port M, Vander Elst L, Corot C, Muller RN. Peptidic targeting of phosphatidylserine for the MRI detection of apoptosis in atherosclerotic plaques. Mol. Pharm. 2009; 6: 1903-1919.


Mots-clés :
  • (Anglais) functionalized iron oxide nanoparticles
  • (Anglais) peptides
  • (Anglais) Parkinson's disease
  • (Anglais) MRI contrast agents
  • (Anglais) apoptosis