The grantee will attempt to develop an immunochemical means of diagnosing and monitoring atheroscerosis. This will be based on a method incorporating blood clearance of radiolabeled antibodies directed against specific constituents of atherosclerotic plaque. For this purpose, a panel of monoclonal antibodies will be prepared against different components of the atherosclerotic plaque. Antibodies against plaque-specific or plaque-associated markers will be selected by comparative immunocytochemical analysis on frozen sections of atherosclerotic and normal arteries from non-human primates and humans. This will enable the identification and selection of antibodies against antigens that are exposed in the lumen of the blood vessel.Monoclonal antibodies against individual plaque antigens will be radiolabeled with 125, and injected into non-human primates for blood clearance studies. To controlilr differences that may exist in the vascular system of different animals, a second radiolabeled monoclonal antibody will be utilized which is known not to bind to antigens in the vascular system. By comparing over time the ratio of these two antibodies in blood, it may be possible to detect specific clearance of the monoclonal antibody that detects antigens within the atherosclerotic plaque. The extent and rate of antibody clearance should be representative of the amount of atherosclerotic plaque in the circulatory system. If successful, this method could be used for early in vivo diagnosis of atherosclerosis and for monitoring the results of therapy in individuals.National Heart, Lung and Blood Institute
