| Research Abstract |
The internal radiation therapy has been exclusively studied since some tumor-specific substances, such as monoclonal antibodies associated with cancer, have been well developed. Comparing with the external radiation therapy, this method is superior in the point that the radiation dose in normal organs should be quite small. However, this theory has not worked out well in clinical practice because radionuclide-conjugates administered are influenced by many factors before they reach tumor sites. The aim of this project is to investigate how some factors infuence the biodisteibution of radionuclide-labeled monoclonal antibodies from pharmacokinetic point of view. As the number of monoclonal antibodies which were used for patients were regulated by the committee, we have not investigated clinical radioimmunodetection enough to evaluate factors which have been studied by experimental animals. neverthless, we have concluded that pharmacokinetic characterization of In-111-labeled anti-CEA mon
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oclonal antibody, ZCE-025 in patients with colorectal cancer were relatively similar each other. Using experimental animals, we have found that injected antibody coupled with the circulating antigens, and thereby became unavailable for reaction with tumor associated antigen, and/or circulating antigen enhanced the degradation of the infected antibody in the plasma before it reached the tumor sites. However, the results obtained from athymic mice were not cases in clinical findings. Circulating antigens have not affected the visualization of tumors, the blood clearance and urine excretion of In-111-ZCE-025. Some other factors, such as vascularity or permeability, which made discrepancies between experimental animals and humans results must be considered very carefully. The fact that the absolute amount of antibody accumulated in tumors of patients was quite small should also be concerned in immunoscintigraphy as well as in radioimmunotherapy. We proposed here that the administration of interferon could improve the localization of antibody in tumors. Several researchers in the U. S. A. have now treated patients who underwent immunoscinitigraphy and/or radioimmunotherapy with interferon under the protocol we proposed. Treatment of iron-chelating agent as well as interferon has incceased the blood clearance of In-111. The interesting results were that effects of iron- or iron-chelating agents on the biodistribution of In-111-ZCE-025 were remarkably different between tumor-bearing and normal mice. This fact should be especially focused on here since similar situation would happen to patients who are on the way to being cured by receiving antibody. We still need investigate not only factors which should influence radioimmunodetection but also mechanisms which should clarify discrepancies of results between from experimental animals and from patients before applying radionuclide-labeled antibody to patients for the purpose of therapy. Less
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