Neuroimaging of vessel amyloid in Alzheimer's disease.
Despite extensive recent advances in understanding Alzheimer's disease (AD) we are unable to noninvasively establish a definite diagnosis during life and cannot monitor the cerebral deposition of amyloid beta protein (A beta) in living patients. We evaluated the use of 10H3, a monoclonal antibody Fab targeting A beta protein 1-28 labeled with Tc-99m. Six subjects with probable AD were studied using single-photon emission computed tomography (SPECT) at times from 0-24 hours following injection. Curves of radioactivity in blood demonstrate a half-life of the injected Fab of 2-3 hours. Images show uptake around the head in the scalp or bone marrow in all subjects. There is no evidence of cerebral uptake of the antibody. Scalp biopsies in all six patients demonstrate diffuse staining with 10H3 of the scalp, a pattern indistinguishable from that found in controls. Evidence of amyloid deposition in the scalp in AD is not seen with other anti-A beta antibodies, suggesting that 10H3 is cross-reacting with another protein. Further studies with anti-A beta antibodies will require longer-lived radionuclides to detect cerebral uptake at later times after injection to allow for complete clearance from the blood. Alternately, imaging using labeled A beta itself may provide a means for noninvasive targeting of cerebral amyloid.
Friedland
R P
RP
Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. rpf2@po.cwru.edu
Kalaria
R
R
Berridge
M
M
Miraldi
F
F
Hedera
P
P
Reno
J
J
Lyle
L
L
Marotta
C A
CA
D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging*; D002536:Cerebral Arteries / Q000000981:diagnostic imaging; D002550:Cerebral Veins / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008297:Male; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015899:Tomography, Emission-Computed, Single-Photon
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; C084358:amyloid beta-protein (1-28)