NR AQWL
AU Sadowski,M.; Pankiewicz,J.; Scholtzova,H.; Tsai,J.; Li,Y.; Carp,R.I.; Meeker,H.C.; Gambetti,P.; Debnath,M.; Mathis,C.A.; Shao,L.; Gan,W.B.; Klunk,W.E.; Wisniewski,T.
TI Targeting prion amyloid deposits in vivo
QU Journal of Neuropathology and Experimental Neurology 2004 Jul; 63(7): 775-84
PT journal article
AB The diagnosis of prion diseases in humans is challenging due to a lack of specific and sensitive non-invasive tests. Many forms of human prion disease including variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and 10% of sporadic CJD cases are associated with amyloid deposition. Several positron emission tomography (PET) ligands have recently been developed to directly image beta-amyloid associated with Alzheimer disease. One of them, methoxy-X04, is a fluorescent derivative of Congo red with high binding affinity toward amyloid fibrils and good blood-brain barrier permeability. Using methoxy-X04, we investigated whether amyloid-targeting ligands can be also employed for direct imaging of amyloid deposits associated with some prion diseases. Such a method could potentially become a novel diagnostic approach for these conditions. Studies were performed on MB mice infected with the 87V mouse-adapted scrapie strain. Labeling of PrP amyloid plaques in brains of presymptomatic and symptomatic mice was demonstrated using in vivo transcranial two-photon microscopy after systemic administration of methoxy-X04. During real-time imaging, PrP amyloid deposits could be clearly distinguished 15 min after intravenous administration of methoxy-X04. The ligand showed rapid clearance from brain areas that did not contain amyloid deposits. PrP amyloid deposits could also be detected by direct application of methoxy-X04 on cerebellar sections from GSS patients. These results suggest that methoxy-X04 or similar derivatives could be used as PET imaging agents to improve the diagnosis of human prion diseases associated with amyloid deposition.
MH Alkenes/*diagnostic use/metabolism/pharmacokinetics; Amyloid beta-Protein/*analysis; Animals; Benzene Derivatives/*diagnostic use/metabolism/pharmacokinetics; Brain/metabolism/pathology; Disease Models, Animal; Human; Metabolic Clearance Rate/drug effects/physiology; Mice; Predictive Value of Tests; Prion Diseases/metabolism/*pathology/*radionuclide imaging; Reproducibility of Results; Scrapie/metabolism/pathology/radionuclide imaging; Senile Plaques/metabolism/*pathology; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tomography, Emission-Computed/*methods
AD Department of Neurology, New York University School of Medicine, New York, New York 10016, USA
SP englisch
PO USA