The aim of this work is to determine the feasibility of using Ga-68 for positron emission tomography by specifically tumor-targeting the nuclide, using bispecific antibody fragments having one arm reactive with tumor antigen and a second arm reactive with a Ga-68 low molecular weight hapten. We will iodine-l25 label an anti-carcinoembryonic antigen complementarity determining region-grafted x murine antidiethylenetriaminepentaacatec acid bispecific F(ab')2 fragment. We will Ga-68 radiolabel a low molecular weight peptide substituted with two diethylenetriaminepentaacatec acid molecules. The agents will be tested in in vitro binding studies to determine binding to each other and tumor antigen. Affinities of the components will be determined. The pretargeting system will be evaluated in vivo using human tumorxenograft models in athymic nude mice and I-l25/Ga-68 dual radiolabeled components. At the end of the Phase I period we aim to have established a method that gives strongly positive tumor-to-all normal organ ratios. Ultimately, we will the combine the strengths of tumor-specific antibody targeting with the sensitivity of positron emission tomography, and with the practical convenience of the gallium-68 generator.
A generally usable system for highly disease-specific and sensitive imaging of cancer would change the paradigm of how the disease is detected and monitored. The specific agents and method we intend to develop under this SBIR, represents an example of such a system. The specific agents of this SBIR are for colon cancer detection, and would have high commercial, potential in this common disease in westernized countries.
