Development and in vitro characterization of a cationized monoclonal antibody against beta A4 protein: a potential probe for Alzheimer's disease.
The blood-brain barrier (BBB) is impermeable to IgG. Therefore, a delivery strategy has to be applied in order to use monoclonal antibodies (mAb) as diagnostic or therapeutic agents in the brain. It has been demonstrated that cationization of IgG allows for the BBB penetration following peripheral administration. A cationized mAb against beta A4-amyloid could be a sensitive and specific diagnostic tool for Alzheimer's disease (AD). The site-protected cationization and radiolabeling with 111In of the specific anti beta-amyloid mAb, AMY33, is described. The binding affinity of the antibody was retained after these procedures (Kd = 3.1 +/- 0.5 nM), as determined by solid-phase immunoradiometric assay and immunocytochemistry on AD brain sections. The in vitro binding by isolated brain capillaries indicated that the cationized antibody may be delivered to the brain in vivo. The ability of the modified antibody to detect cerebral beta-amyloid deposits in vivo can now be evaluated using single photon emission computed tomography (SPECT) and a suitable animal model for cerebral amyloidosis, such as non-human primates or aged canines.
Department of Medicine, UCLA School of Medicine 90024.
U
U
Bickel
V M
VM
Lee
J Q
JQ
Trojanowski
W M
WM
Pardridge
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D002412:Cations; D002417:Cattle; D005260:Female; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000737:chemistry; D007150:Immunohistochemistry; D015592:Immunoradiometric Assay; D007205:Indium Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D002412:Cations; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D004369:Pentetic Acid