The purpose of this application is to extend work that Summa Medical Corporation (SMC) has performed in the area of radioimunnoimaging (RII) with Tc-99m labeled antibodies for the in vivo detection of human malignancy using external gamma scintigraphy. SMC has conducted clinical trials in Vancouver, BC (Canada) under the first known and approved IND application for the use of Tc-99m labeled antibodies to human chorionic gonadotropin (hCG) using affinity pufified sheep polyclonal and murine monoclonal IgG antibodies and F(ab')2 fragments. SMC has developed a new technique for the radiolabeling of antibodies and antibody fragments with Tc-99m that is suitable for the clinical studies and is reducible to instant labeling of """"""""cold"""""""" kits. The results of these studies have been very encouraging in that a significant percentage of human tumors expressing hCG have been demonstrated at diverse sites in the body using the RII technique. However, the sensitivity of this technique may be improved by increasing the total percentage of radio nuclide injected that specifically targets to tumor sites. Therefore, SMC is applying under the SBIR program to test a novel approach termed radioimmunoamplification that seeks to increase the sensitivity of the RII technique. In the present application, a double antibody approach is to be tested using appropriate monoclonal antibodies directed against tumor associated antigens, followed by the administration after an appropriate time interval of a second antibody that will be radiolabeled with Tc-99m that should target to the first antibody. Two separate animal models will be employed, including an anti-idiotype system, and a human tumor that expresses hCG that will be grown in nude mice. SMC will also study the in vivo localization of human monoclonal antibodies reactive with hCG and labeled with Tc-99m in this latter model. Potential immunopathology resulting from the formation of immune complexes in vivo will also be assessed. The results of these studies will have direct bearing on whether this type of approach will be attempted in human clinical trials. These studies may lead to the development of commercially viable products demonstrating significant advantage over current approaches to RII.
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