We propose to study whether a second antibody (SA) will be able to improve radioimmunodetection of cancer with a primary radiolabeled anticancer antibody (PA). Preliminary studies indicate that a second antibody reduces circulating radiolabeled primary antibody, thereby improving tumor/blood, as well as tumor/nontarget tissue ratios. Studies are proposed to answer questions concerning the dose of SA and time interval following the injection of the primary antibody required to optimize tumor imaging. For all of these studies PA and SA fragments (F(Ab')2 and Fab') will be evaluated in order to assess the role of the Fc portion of the IgG on the clearance of the radiolabeled PA by the SA and as a means of directly comparing the efficacy of tumor localizing PA fragments above to the SA approach. Our preliminary data have already suggested the SA approach using anti-immunoglobulin antibody may be useful clinically for detecting tumors by external imaging. Thus, we propose in the latter portion of the second year to initiate clinical trials using the conditions determined by experimentation in the animal model. In addition, we plan to investigate whether radiolabeled SA administered after injection of radiolabeled PA can amplify tumor radioactivity but still reduce the total blood pool background. Finally, we intend to study the influence of the SA on suppressing anti-primary immunoglobulin antibody formation or if the presence of circulating anti-primary immunoglobulin interferes with radioimmunodetection of cancer. Thus, the overall proposal will address several topics that will refine our understanding of some of the factors that influence the detection of tumors by radiolabeled antibody and possible ways to improve this methodology.
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