Myocardial infarction monoclonal antibodies

Various antibody preparations have been developed that facilitate imaging of vascular-related conditions, including myocardial infarction, deep vein thrombosis and atherosclerosis. Anti-myosin monoclonal antibody fragments (Fab) labelled with mIn, for example, have been used for imaging purposes in conjunction with a planar gamma camera. The antibody displays specificity for intracellular cardiac myosin, which is exposed only upon death of heart muscle tissue induced by a myocardial infarction (heart attack). 

Lefkovits J, Ivanhoe RJ, Califf RM, et al. Effects of platelet glycoprotein llb/llla receptor blockade by a chimeric monoclonal antibody on acute and six-month outcomes after percutaneous transluminal coronary angioplasty for acute myocardial infarction (EPIC). Am J Cardiol 1996 77 1045-1051. 

Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody used in the treatment of chronic lymphocytic leukemia and T-cell lymphoma. It targets CD52, a protein present on the surface of mature lymphocytes. Alemtuzumab has been associated with infusion-related events including hypotension, rigors, fever, shortness of breath, bron-chospasm, chills, and/or rash. Also reported were syncope, pulmonary infiltrates, cardiac arrhythmias, myocardial infarction and cardiac arrest. 

Bodor GS, Porter S, Landt Y, et al. Development of monoclonal antibodies for an assay of cardiac troponin-I and preliminary results in suspected cases of myocardial infarction. Clin Chem 38 2203-2214,1992. 

Amsterdam EA, Stahl GL, Pan H-L, Rendig SV, Fletcher MP, Lon-ghurst JC (1995) Limitation of reperfusion injury by a monoclonal antibody to C5a during myocardial infarction in pigs. Am J Physiol 268 H448-H457. 

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)...

Two immunosensors developed by O Regan et al. [89,90] have demonstrated their usefulness for the early assessment of acute myocardial infarction (AMI). Human heart fatty-acid binding protein (H-FABP) is a biochemical marker for the early assessment of AMI. The authors constructed an amperometric immunosensor for the rapid detection of H-FABP in whole blood. The sensor is based on a one-step, direct sandwich assay in which the analyte and an alkaline phosphatase (AP) labelled antibody are simultaneously added to the immobilized primary antibody, using two distinct monoclonal mouse anti-human H-FABP antibodies. The substrate p-amino-phenyl phosphate is converted to p-aminophenol by AP, and the current generated by its subsequent oxidation at +300 mV vs. Ag/AgCl is measured. The total assay time is 50 min, and the standard curve was linear between 4 and 250 ng ml . The intra- and inter-assay coefficients of variation were below 9%. No cross-reactivity of the antibodies was found with other early cardiac markers, and endogenous substances in whole blood did not have an... 

Monoclonal antibodies to GPlIb/IIIa receptors are effective inhibitors of platelet function. Animal studies suggest that they may reduce both the dose, and the delay in onset of thrombolytic effect with streptokinase and similar agents when they are used in treating the sequelae of myocardial infarction. Early trials in humans suggest that these agents will be valuable for some specialist applications. 

Biotechnology-derived products may be classified into monoclonal antibodies, gene therapy, vaccines, enzymes, and interleukins. The current major therapeutic areas for these substances are cancer or cancer-related conditions, AIDS or HIV-related disease, diabetes, human growth hormone, myocardial infarction, and inflammatory disease. 

Serum Mn-SOD levels were determined in 29 patients with acute myocardial infarction by an ELISA using a monoclonal antibody (S20). Figure 17 shows typical changes in serum Mn-SOD in two patients following acute myocardial infarction. Case A is an example of a successful reperfusion of the infarcted vessel at an acute stage, and case B is a case without reperfusion. In both instances a biphasic elevation of Mn-SOD is noted—a small early one that is slightly higher... 

K5. Kawaguchi, T., Suzuki, K., Matsuda, Y., Nishiura, T., Uda, T., Ono, M., Sekiya, C., Ishikawa, M., lino, S., Endo, Y., and Taniguchi, N., Serum Mn-superoxide dismutase Normal values and increased levels in patients with acute myocardial infarction and several malignant diseases determined by enzyme-linked immunosorbent assay using a monoclonal antibody. J. Immunol. Methods 127, 249-254 (1990). 

Khaw, B. A. (1994) Antimyosin antibody for the diagnosis of acute myocardial infarction experimental validation, in Monoclonal Antibodies in Cardiovascular Diseases (Khaw, B. A., Narula, J., and Strauss, H. W., eds.), Lea and Febiger, Malvern, PA, pp. 15-29. 

Khaw, B. A., Mattis, J. A., Melincoff, G., Strauss, H. W., Gold, H. K and Haber, E. (1984) Monoclonal antibody to cardiac myosin scintigraphic imaging of experimental myocardial infarction. Hybridoma 3, 11-23. 

Abciximab (ReoPro) is the Fab fragment of a humanized monoclonal antibody directed against the a bp3 receptor. It also binds to the vitronectin receptor on platelets, vascular endothelial cells, and smooth-muscle cells. The antibody is used in conjunction with percutaneous angioplasty for coronary thromboses, and when used in conjunction with aspirin and heparin, has been shown to be quite effective in preventing restenosis, recurrent myocardial infarction, and death. 

Kleiman NS, Ohman EM, Califf RM, George BS, Kereiakes D, Aguirre FV, Weisman H, Schaible T, Topol EJ. Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Eab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMl) 8 Pilot Study. J Am CoU Cardiol. 1993 22 381-389. 

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