Monoclonal antibodies specific for human cardiac myosin: selection, characterization and experimental myocardial infarct imaging

Abstract

Radiolabelled anti-myosin antibodies (AM Ab) specifically accumulate in necrotizing myocytes and, therefore, allow the scintigraphic detection of myocardial infarction. In order to provide a constant supply of myosin-specific antibodies, the somatic cell fusion technique was used for the selection and propagation of AM Ab. Out of 126 antibody producing cell lines, nine were selected for further subcloning, due to their high affinity for purified myosin. For the in vivo imaging, two IgG-antibody molecules appeared particularly useful based on their antigenic specificity as assessed by immunoblotting and indirect immunofluorescence technique. After radiolabelling with iodine-123, undigested antibody molecules or their Fab fragments were injected into 10 dogs with experimental myocardial infarction. The accumulation of radioactivity in myocardial infarction was assessed by in vivo imaging and in vitro scintigraphy of ventricular slices stained by tetrazolium. The use of undigested AM Ab resulted in a high uptake ratio of radioactivity in the infarcted as compared to normal myocardium (20:1). In vivo infarct imaging, however, was not possible due to sustained labelling of the blood pool. The uptake ratio of iodine-123 labelled Fab fragments was only 9:1, but due to a faster plasma clearance of the Fab fragments, uptake in the heart could be visualized 5 h after intravenous injection. Clear differentiation between infarcted and noninfarcted myocardium, however, was limited by accumulation of radioactivity in the thoracotomy wound, in the liver, and in the stomach.