DESCRIPTION (provided by applicant): The objective of this work is to develop a set of reagents that together comprise a new imaging system for detection of cancer, in its early, its metastatic, and its recurrent stages. Early detection, better treatment choices and new information that save uneccessary surgeries and treatments are long-term aim of this work. The reagents in this project will be developed for the colo-rectal cancer indication, but the same targeting and detection principles will be broadly applicable, and can be extended later to any cancer type. Use of molecularly targeted reagents will be combined with the most senstitive imaging modality, positron emission tomography. This SBIR Phase I application will explore the feasibility of using a bispecific antibody construct, targeted against the carcinoembryonic antigen, and up-regulated in many cancers, as an agent to selectively place a secondary binding arm specifically at sites of disease. Once circulating bispecific antibody has cleared normal tissue and maximized at tumor sites, a secondary recognition hapten recognized by tumor-localized bispecific antibody will be administered. This secondary recognition hapten will be radiolabeled with gallium-68, a positron-emitting radionuclide, and will be molecularly designed to rapidly flush from the living system if not bound at the sites of disease. Such an approach is expected to result in very high tumor to background ratios with regard to all major internal organs, and combined with the exceptional sensitivity of positron emission tomographic imaging of the tumor-localized gallium-68 radionuclide, comprizes a unique opportunity to significantly enhance specifc imaging of this disease. In this Phase I work feasibility will be shown by preparation and combination of the various components of the imaging system, together with demonstration of the method through the stage of preclincal testing in an appropriate animal model of human colon cancer. SBIR Phase II will support the effort to extend the system into a human clincial trial, to expedite the methodology into clincial application as soon as possible. With success, SBIR Phase II will concentrate on the effort to obtain Food and Drug Administration approval of the imaging methodology and to commercialize the agents to improve diagnosis and therapy of CEA positive tumors.