We have recently developed what may become the optimum method of covalently coupling strong chelating groups such as DTPA to proteins. We have shown that albumin may be coupled in minutes at neutral pH with up to 70% efficiency, and that the 111In-labeled product distributes in vivo identically to radioiodinated albumin. Furthermore, both in vitro and in vivo tests of the viability of fibrinogen coupled in this manner show that clotability of the protein is not affected. Positive images of forming clots obtained in dogs support this claim. Recently, we have applied this method to IgG antibodies, proteins with considerable potential for tumor imaging particularly since the development of hybridoma technology. Coupling efficiencies of 40 (plus/minus) 5% were obtained for all the polyclonal and monoclonal antibodies studied. After coupling with DTPA and labeling with 111In, monoclonal antiCEA antibody retains its ability to bind to its antigen both in vitro and in vivo. In nude mice, 40% I.D./g of the radiolabel localizes in a human colorectal xenograph at 24 hrs. compared to 9% for control antibody and 19% for radioiodinated anti-CEA antibody. We now wish to expand upon these preliminary studies by investigating in detail the parameters of DTPA coupling to intact antibody and to IgG fragments, the in vivo stability of the label, the kinetics of uptake of the labeled antibodies in the nude mouse model, the localization properties of different polyclonal and monoclonal antibodies labeled by our method, etc. We expect that this systematic study will result in the development of a new and attractive method of radiolabeling antibody and will, at the same time, provide information on the advantages of monoclonal antibody for tumor imaging.
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