Application of Radiolabeled Monoclonal A7 Antibody for Radioimmunotherapy of Human Colon Cancer

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Using monoclonal antibody specific for tumor associated antigen expressed on human malignant tumor cells, therapeutic radionuclides can be delivered to the tumor lesion in vivo. For this approach, the stable radiometal chelates is required. Re-186 or Re-188 are expected to be the choice of radionuclide for radioimmunotherapy. We have assessed the conjugation procedure of the MAG3 chelate and HYNIC chelate. The stability of the radiolabel was found to be satisfactory. A monoclonal antibody A7 was used for the project. This antibody recognizes adenocarcinoma related antigen on the variety of human colon cancer cells. The A7 antibody was labeled with Re-186, resulting in the specific activity of greater than 37 MBq/mg. And the immunoreactivity of the labeled antibody was 67%, which is equivalent for that of I-131 labeled counterpart.LS180 human colon cancer cells were inoculated to the Balb/c nude mice. In vivo imaging with either I-131 or Re-186 labeled A7 provided well-delineated tumor. Therapy trial study demonstrated that Re-186 A7 delivered 1.6 times higher radiation to the tumor than I-131 A7. Thus, Re-186 antibody should be the attractive modality for radioimmunotherapy.We have tried to increase the tumor uptake of radiolabeled antibodies by modifying the delivery system to the tumor tissue. The combination usage of angiotensin-II and a kininase inhibitor, enalapril maleate, increased the mouse blood pressure from 95/61 to 153/67. And the tumor uptake was also increased by the factor of 1.62 with little change in normal organ distribution. In conclusions, enhanced tumor uptake was achieved by manipulating hemodynamics and vascular permeability of the tumor tissue and this technique can be applied for effective targeting.