Four mouse monoclonal antibodies strongly reactive with human colon cancer and weakly or not at all with normal human colon, other normal human tissues, and RBCs and WBCs have been developed in our laboratory. None of these cross-react with CEA, and the targeted antigens appear distinct from other described colon cancer enriched antigens. One of these, MAb 1A3, has been extensively characterized and remains a prime candidate for clinical tumor imaging trials. MAbs 1A3 will be extensively studied in the GW39 human colon cancer hamster model to determine if the use of MAb fragments, or novel chelating agents, or the saturation of rapid metabolic uptake mechanisms can reduce the high liver background currently seen when (111 In)- anti-cancer MAbs are used for imaging tumors. This problem is critical when designing strategies for imaging metastases to the liver. An additional goal is to evaluate the imaging potential of positron emitting radionuclides, (68Ga) and (18F), linked to MAb 1A3 or its fragments in our animal model. For each immunoreactive reagent, dose response curves and biodistributions studies will be done. We propose to initiate clinical studies in colorectal cancer patients in the latter half of this study using the best reagent in terms of tumor localization properties, including rapid liver clearance, overall tumor/non- tumor ratios and success in imaging colon tumors localized in the hamster model (including tumor implants in the liver). Clinical studies will proceed in 2 stages: the first involving 15 patients with known metastasis; the second involving 50 patients with resectable primary colon tumors. These clinical trails will compare the accuracy of the radiolabeled MAb as a tumor imaging reagent to conventional staging and localization techniques. Throughout the course of these studies, further in vitro and in vivo studies with each of our MAbs linked to radionuclides will continue in the hopes of defining a second reagents for use in future studies involving combinations of MAbs.
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