Scintigraphic detection of early cardiac rejection by iodine 123-labeled monoclonal antibody directed against monomorphic determinant of major histocompatibility complex class II antigens

Abstract

Although it has been shown that early cardiac rejection can be visualized by radioimmunoscintigraphy targeting major histocompatibility complex class II antigen, the use of antibodies that bind to a polymorphic determinant of class II antigen has certain disadvantages for clinical application. This investigation was designed to examine the feasibility of scintigraphic detection of cardiac allograft rejection by using a monoclonal antibody that reacts with a monomorphic determinant of rat IA antigens. Twenty PVG rats (RT1 c) and five DA rats (RT1 a) underwent heterotopic transplantation with DA hearts. Two of the 20 allografted rats were treated with FK506 (2 mg/kg/day). Seventeen rats were injected intravenously with 80 μCi of iodine 123-labeled monoclonal antibody reactive with a monomorphic determinant of rat major histocompatibility complex class II antigens (Ox6) 16 hours before scintigraphy, and images were compared with those obtained by injection of 123I-labeled monoclonal antibody against a polymorphic determinant of class II antigens (F17-23-6, anti-RT1 a) (n = 8). Background activity was higher in rats injected with Ox6 than in rats injected with F17-23-6. Uptake of labeled Ox6 in the grafts reflected the severity of rejection as determined by histopathologic criteria. Rejecting allografts with lymphocyte infiltration but without myocyte necrosis could be identified by the scintigraphy with use of labeled Ox6. The ratios of radioactivity in the graft to radioactivity in the blood (percent injected dose per gram of tissue) in rats with grade IA and IB rejection (0.56 ± 0.12, n = 4, p < 0.001) and in rats with grade IIIA and IIIB rejection (0.60 ± 0.09, n = 4, p < 0.001) were significantly greater than in rats with nonrejecting grafts (0.24 ± 0.08, n = 9). In conclusion, radioimmune scintigraphy with use of 123I-labeled monoclonal antibody directed against a monomorphic determinant of major histocompatibility complex class II antigen appears to be a sensitive and noninvasive method for detecting cardiac allograft rejection.