Pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody in murine experimental viral myocarditis.
The pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody Fab were investigated with use of murine experimental viral myocarditis as a model. The biodistribution of indium-111-labeled antimyosin antibody Fab on days 3, 5, 7, 14, 21 and 28 after encephalomyocarditis virus inoculation demonstrated that myocardial uptake increased significantly on days 5, 7 and 14 (maximum on day 7) in infected versus uninfected mice (p less than 0.001). In vivo kinetics in infected mice on day 7 demonstrated that the heart to blood ratio reached a maximum 48 h after the intravenous administration of indium-111-labeled antimyosin Fab, which was considered to be the optimal time for scintigraphy. The scintigraphic images obtained with indium-111-labeled antimyosin Fab demonstrated positive uptake in the cardiac lesion in infected mice. The pathologic study demonstrated that myocardial uptake correlated well with pathologic grades of myocardial necrosis. High performance liquid chromatography revealed the presence of an antigen-antibody complex in the circulation of infected mice after the injection of indium-111-labeled antimyosin Fab. This antigen bound to indium-111-labeled antimyosin Fab in the circulation might be whole myosin and this complex may decrease myocardial uptake and increase liver uptake. It is concluded that indium-111-labeled antimyosin monoclonal antibody Fab accumulates selectively in damaged heart tissue in mice with acute myocarditis and that indium-111-labeled antimyosin Fab scintigraphy may be a useful method for the visualization of acute myocarditis.
Yamada
T
T
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Matsumori
A
A
Watanabe
Y
Y
Tamaki
N
N
Yonekura
Y
Y
Endo
K
K
Konishi
J
J
Kawai
C
C
D000818:Animals; D000911:Antibodies, Monoclonal; D002851:Chromatography, High Pressure Liquid; D004686:Encephalomyocarditis virus; D004769:Enterovirus Infections / Q000000981:diagnostic imaging* / Q000382:microbiology; D006321:Heart / Q000000981:diagnostic imaging*; D007205:Indium Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000000981:diagnostic imaging* / Q000382:microbiology; D009218:Myosins / Q000276:immunology*; D009942:Organometallic Compounds; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; C058899:imciromab pentetate; D009218:Myosins