Anti-amyloid-β-mediated positron emission tomography imaging in Alzheimer's disease mouse brains

• Published in: PloS one 2012-12, Vol.7 (12), p.e51958-e51958
• Main Authors: McLean, Daniel, Cooke, Michael J, Wang, Yuanfei, Green, David, Fraser, Paul E, George-Hyslop, Peter St, Shoichet, Molly S
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - diagnosis; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - immunology; Amyloid beta-Peptides - metabolism; Animals; Antibodies; Antibodies - chemistry; Antibodies - immunology; Antibodies - pharmacology; Apolipoproteins; Biology; Biomedical engineering; Biomedical materials; Biophysics; Blood-brain barrier; Blood-Brain Barrier - pathology; Brain; Brain - metabolism; Brain - pathology; Brain research; Chemical engineering; Chemistry; Copper; Dementia; Diagnostic systems; Disease Models, Animal; Emissions; Emissions control; Engineering; Humans; Imaging techniques; Immunoglobulin G - chemistry; Immunoglobulin G - immunology; Immunoglobulin G - pharmacology; Immunoglobulins; Ligands; Lipoproteins; Medical imaging; Medicine; Mice; Mice, Transgenic; Neurodegeneration; Neurodegenerative diseases; Neuroimaging; Neurology; Neurosciences; NMR; Nuclear magnetic resonance; Oligomers; Osmotic Pressure; Permeability; Polyamines; Polyethylene glycol; Positron emission tomography; Protein Binding; Proteins; Rabbits; Rodents
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0051958

Antibody-mediated imaging of amyloid β (Aβ) in Alzheimer's disease (AD) offers a promising strategy to detect and monitor specific Aβ species, such as oligomers, that have important pathological and therapeutic relevance. The major current limitation of antibodies as a diagnostic and imaging device is poor blood-brain-barrier permeability. A classical anti-Aβ antibody, 6E10, is modified with 10 kDa polyethylene glycol (PEG) and a positron emitting isotope, Copper-64 (t(½) = 12.7 h), and intravenously delivered to the TgCRND8 mouse model of Alzheimer's disease. Modification of 6E10 with PEG (6E10-PEG) increases accumulation of 6E10 in brain tissue in both TgCRND8 and wild type control animals. 6E10-PEG differentiates TgCRND8 animals from wild type controls using positron emission tomography (PET) and provides a framework for using antibodies to detect pathology using non-invasive medical imaging techniques.