Myocardial uptake of 111In monoclonal antimyosin Fab in detecting doxorubicin cardiotoxicity in rats. Morphological and hemodynamic findings.

Abstract

The therapeutic value of doxorubicin (DOX) is limited by its cardiotoxicity, which is dose dependent. To improve the detection of such myocardial damage, this study was designed to determine whether the 111In antimyosin antibody Fab could serve as a marker for cardiotoxicity in treated versus control rats on the basis of comparative morphological and hemodynamic findings. DOX was administered by intravenous injection to rats at a dose of 3 mg.kg-1.week-1 for 5 weeks. Three weeks after the final injection, an intravenous dose of 111In antimyosin, 740 kBq (20 microCi), was administered, and tissue distribution of the radioisotope (percent kilogram dose per gram) was assessed in 48 hours. Myocardial uptake of radioactivity by both ventricles was more prominent in the DOX-treated rats than in control rats (p < 0.001). The heart-to-blood and heart-to-lung uptake ratios were markedly higher in the treated rats than in controls (p < 0.001). As the severity of the myocardial damage increased, there was a progressive increase in myocardial uptake. There was a strong correlation between the severity of myocardial damage and the ventricular end-diastolic pressure (r = 0.84 and r = 0.83 in the left and right ventricles, respectively). On microscopic immunoautoradiography of the DOX-treated heart, there was a specific immunolocalization of the radiotracer in the injured myocytes but no radioactivity in the control myocytes. 111In antimyosin antibody appears to be a useful immunoradiotracer in detecting cardiac damage induced by DOX administration and in assessing the severity of cardiotoxicity. These data reinforce the clinical observation that myocardial imaging using 111In antimyosin Fab is able to provide information to guide the course of patients receiving DOX treatment.