Anti-Amyloid-beta-Mediated Positron Emission Tomography Imaging in Alzheimer's Disease Mouse Brains

作者:McLean Daniel; Cooke Michael J; Wang Yuanfei; Green David; Fraser Paul E; St George Hyslop Peter; Shoichet Molly S*
来源:PLos One, 2012, 7(12): e51958.
DOI:10.1371/journal.pone.0051958

摘要

Antibody-mediated imaging of amyloid beta (A beta) in Alzheimer's disease (AD) offers a promising strategy to detect and monitor specific A beta 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-A beta antibody, 6E10, is modified with 10 kDa polyethylene glycol (PEG) and a positron emitting isotope, Copper-64 (t(1/2) = 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.