Antimyosin Fab

Trubetskoy, V.S., Narula, J., Khaw, B.A., and Torchilin, V.P. (1993) Chemically optimized antimyosin Fab conjugates with chelating polymers Importance of the nature of the protein-polymer single site covalent bond for biodistribution and infarction localization. Bioconjugate Chem. 4, 251-255. 

The application of antibodies in cardiovascular targeting in vivo originated with the experimental demonstration of the feasibility of using radiolabeled antimyosin antibody for diagnosis of acute myocardial infarction in 1976. Since then, the use of antibodies in the cardiovascular system has encompassed imaging of myocarditis,heart transplant rejection, dilated cardiomyopathy, alcohol induced cardiomyopathy,adriamycin cardiotoxicity, various other cardiomyopathies, vascular clots, atherosclerotic lesions,and even certain cancers such as soft tissue sarcomas.f Yet the best characterized and studied antibody for cardiovascular diagnostic targeting is monoclonal antimyosin Fab for its exquisite specificity... 

Fig. 2 Gamma images of four dogs with acute experimental myocardial infarction, injected with high affinity In-labeled antimyosin Fab (Ka = 0.5-1 x 10 L/M) (A and C), In-labeled non-specific monoclonal Fab (B) and the low affinity In labeled 3H3 antimyosin Fab (Ka = 5 x 10 L/M) (D). At 5h post intravenous administration of these antibodies, only the images with high affinity antimyosin showed unequivocal infarct uptake, whereas the images with non-antimyosin specific monoclonal Fab and the low affinity antimyosin Fab showed only blood pool activity. (From Ref. l)...

Fig. 3 Anterior and 45° LAO images of two patient with acute MI at 24 and 26 h after intravenous administration of In-111 labeled antimyosin Fab. Images of a patient with persistently occluded LAD (no reperfusion) (A) and those of a patient with successful reperfusion (B). (From Ref 1)...

Fig. 4 Serial left lateral gamma images of two dogs with acute experimental myocardial infarction injected with negative charge-modified In-111 labeled antimyosin Fab (right panels) and conventionally In-111 labeled antimyosin Fab (left panels) A and B = 30 min images, C and D = 1 h, E and F = 2h, and G andH = 3h post intravenous...

Fig. 5 Normal myocardial activity of polymer modified antimyosin Fab and conventionally In-111 labeled antimyosin Fab. (From Ref °l)...

Fig. 6 Left lateral gamma image of a rabbit with a 216 mg experimental myocardial infarct visualized with In-111 labeled negative charge-modified antimyosin Fab. Arrow points to the small infarct visualized in vivo. (From Ref...

Due to the mechanism of targeting of antimyosin Fab, it appears that antimyosin could also be used to delineate various cardiomyopathies as long as there is an association of the disease process with irreversible myocardial injury where the integrity of the cell... 

Kairemo, K.J. Wiklund, T.A. Liewendahl, K. Imaging of soft-tissue sarcomas with in-lll-labeled monoclonal antimyosin fab fragments. J. Nucl. Med. 1990, 31, 23-31. 

Khaw, B.A. Yasuda, T. Gold, H.K. Leinbach, R.C. Johns, J.A. Kanke, M. Barlai-Kovach, M. Strauss, H.W. Haber, E. Acute myocardial infarct imaging with indium-ill-labeled monoclonal antimyosin fab. J. Nucl. Med. 1987, 28, 1671-1678. 

Frist, W. Yasuda, T. SegaU, G. Khaw, B.A. Strauss, H.W. Gold, H.K. Stinson, E. Oyer, P. Baldwin, J. BiUingham, M. McDougall, R. Haber, E. Non-invasive detection of human cardiac transplant rejection with in antimyosin (Fab) imaging. Circulation 1987, 76, V81-85. 

Carrio, I. Diagnosis of doxorubicin cardiotoxicity with indium-111 antimyosin fab. In Monoclonal Antibodies in Cardiovascular Diseases Khaw, B.A., Narula, J., Strauss, H.W., Eds. Lee Eebiger Philadelphia, 1994 99-108. 

Fig. 2. (A) Left lateral gamma images of dogs with acute experimental MI. Images a, c, e, and g were obtained after iv administration of conventionally modified " In-DTPA-antimyosin Fab (AM-Fab) images b, d, f, and h were obtained after administration of AM-Fab modified with 11 In-loaded chelating polymer (PL-AM Fab). The heavy load of chelating polymer-modified AM Fab with reporter radiometal permits one to obtain a clear infarct image in the left lateral oblique position only in 3 h (bright spot on image h). Whereas the use of traditionally labeled antibody requires <24 h to yield images of a comparable quality. From ref. 21.

Antimyosin Fab was labeled with 125I and 123I by the Iodogen iodination method (61) because of its gentler nature of compared to chloramine T. Free and AM-bound radioactivity were separated as described above. 

Nakata, T., Sakakibara, T., Noto, T Shoji, T., Tsuda, T Kubota, M Hattori, A., and Iimura, O. (1991) Myocardial distribution of indium-111 antimyosin Fab in acute inferior and right ventricular infarction comparison with Tc-99m pyrophosphate imaging and histological examination. J. Nucleic Med. 32, 865-867. 

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