Development of an anti-A beta monoclonal antibody for in vivo imaging of amyloid angiopathy in Alzheimer's disease.
We evaluated the efficacy of murine monoclonal antibodies (MAbs) targeted to the A beta amyloid of Alzheimer's disease for development of procedures for the in vivo identification of amyloid angiopathy (AA). MAbs to A beta were prepared and screened for effectiveness in visualizing AA and neuritic plaques in postmortem AD brain sections. They were assessed again after enzymatic cleavage to produce Fab fragments and after labeling with technetium-99m (99mTc) using a diamide dimercaptide ligand system. Modified and radiolabeled Fab fragments retained activity and specificity toward amyloid-laden blood vessels and neuritic plaques. A highly specific murine MAb, 10H3, was identified and characterized that fulfills criteria necessary for the development of an in vivo diagnostic imaging agent. Toxicity studies in rats showed the MAb to be safe. Biodistribution studies in mice demonstrated desirable properties for use as an imaging agent. Expansion and adaptation of these strategies may provide the methods and materials for the noninvasive analysis of AA in living patients, and permit assessment of the contribution of AA to the clinical and pathological features of AD.
Friedland
R P
RP
Department of Neurology, Case Western Reserve University, Cleveland, OH 44106.
Majocha
R E
RE
Reno
J M
JM
Lyle
L R
LR
Marotta
C A
CA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000032:analysis*; D000818:Animals; D000911:Antibodies, Monoclonal; D001923:Brain Chemistry; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016719:Radioimmunodetection; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D000911:Antibodies, Monoclonal