VECTOR-MEDIATED DELIVERY OF I-125 LABELED BETA-AMYLOID PEPTIDE A-BETA(1-40) THROUGH THE BLOOD-BRAIN-BARRIER AND BINDING TO ALZHEIMER-DISEASE AMYLOID OF THE A-BETA(1-40) VECTOR COMPLEX/

The brain amyloid of Alzheimer disease (AD) may potentially be imaged in patients with AD by using neuroimaging technology and a radiolabele d form of the 40-residue beta-amyloid peptide A beta(1-40) that is ena bled to undergo transport through the brain capillary endothelial wall , which makes up the blood-brain barrier (BBB) in vivo. Transport of I -125-labeled A beta(1-40) (I-125-A beta(1-40)) through the BBB was fou nd to be negligible by experiments with both an intravenous injection technique and an internal carotid artery perfusion method in anestheti zed rats. In addition, I-125-A beta(1-40) was rapidly metabolized afte r either intravenous injection or internal carotid artery perfusion, B BB transport was increased and peripheral metabolism was decreased by conjugation of monobiotinylated I-125-A beta(1-40) to a vector-mediate d drug delivery system, which consisted of a conjugate of streptavidin (SA) and the OX26 monoclonal antibody to the rat transferrin receptor , which undergoes receptor-mediated transcytosis through the BBB. The brain uptake, expressed as percent of injected dose delivered per gram of brain, of the I-125,bio-A beta(1-40)/SA-OX26 conjugate was 0.15 +/ - 0.01, a level that is 2-fold greater than the brain uptake of morphi ne. The binding of the I-125,bio-A beta(1-40)/SA-OX26 conjugate to the amyloid of AD brain was demonstrated by both film and emulsion autora diography performed on frozen sections of AD brain. Binding of the I-1 25,bio-A beta(1-40)/SA-OX26 conjugate to the amyloid of AD brain was c ompletely inhibited by high concentrations of unlabeled A beta(1-40), In conclusion, these studies show that BBB transport and access to amy loid within brain may be achieved by conjugation of A beta(1-40) to a vector-mediated BBB drug delivery system.