NR AXWX
AU Song,P.J.; Bernard,S.; Sarradin,P.; Barc,C.; Vergote,J.; Chalon,S.; Kung,M.P.; Kung,H.F.; Lantier,F.; Guilloteau,D.
TI Imaging Probes for Prion Detection
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.163
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Objective: Prion diseases are characterized neuropathologically by deposits of prion protein amyloid fibrils (PrPsc) in brain. These cerebral amyloid deposits are colocalized with a microglia mediated chronic inflammatory response. In this study, we examined the possibility of 6-iodo-2-(4-dimetylamino-)phenyl-imidazo[1,2-a]pyridine (IMPY): a ß-
amyloid probe and the peripheral benzodiazepine probe PK11195, for imaging of progressive prion deposits and activated microglia in a scrapie-infected mice model.
Materials and methods: Scrapie-infected mice model was obtained by intracerebral infection with C506-M3 scrapie strain homogenate in C57BL/6J mice. The binding of [125I]IMPY and [3H]PK11195 to prion deposits and activated microglia were evaluated by in vitro autoradiography on brain frozen sections of 20 µm at different time points postinoculation (dpi). Plaque binding was confirmed by histoblots with prion proteinspecific monoclonal antibody 2D6.
Results: Detection of prion deposits, colocalized with activated microglia as early as 60 days dpi, in the right thalamus. The staining spread then asymmetrically to the hippocampus and cortex at 90 days dpi. At 120 and 150 days dpi, an intense and widespread binding of [125I]IMPY and [3H]PK11195 were observed on infected mice brain sections. Radiolabelled regions of [125I]IMPY are consistent and correlated with the signals obtained by histoblots staining. Similar labelling performed with [125I]IMPY and [3H]PK11195 on normal brain sections showed no specific binding.
Conclusion: These observations indicate that a colocalisation of PrPsc deposition and activated microglia can be detected at 60 days dpi, by using imaging technique with [125I]IMPY and [3H]PK11195 in the course of prion disease in scrapie-infected mice. Use of these probes to detect in vivo prion disease is in progression.
Acknowledgements: This study was supported by grants from Association France Alzheimer, European DiMI and IFR135.
AD P.J. Song, J. Vergote, S. Chalon, D. Guilloteau, Universite Francois-Rabelais, INSERM U619, France; S. Bernard, P. Sarradin, C. Barc, F. Lantier, INRA, IASP UR1282, France; M.P. Kung, H.F. Kung, University of Pennsylvania, Department of Radiology, USA
SP englisch
PO Schottland