Metal decomposition rates of 111In-DTPA and EDTA conjugates of monoclonal antibodies in vivo.

We have studied the metal chelate decomposition rates in vivo in both 111In-labelled benzyl EDTA and DTPA (bicyclic anhydride) conjugates of monoclonal anti-IAk IgG2a with identical Ka = 1 X 10(11)M-1 in both Ag+ve and Ag-ve mice. Twenty mu Ci was given i.v. and whole body counting done immediately and daily for 10 days, with six to eight mice in each group. Half the mice in each group received i.p. injections of 5.0 mg CaNa2 EDTA chase (Versenate) to facilitate urinary excretion of free 111In. 50% of control 111In-citrate remained at nine days but only 8% with chase. No significant loss of 111In with chase occurred with C1 substituted EDTA conjugates. A 19% increase in excretion was demonstrated with the chase in mice given DTPA conjugates (1.9% per day). While this will not interfere with radioimmunoimaging up to 24 h after injection, waiting periods of a week or longer will produce significant background of free 111In in the reticuloendothelial system, RES. 111In-EDTA stability was important in accurate metabolic rate measurements of anti-IAk; T1/2 = 7.0 days in Ag-ve mice, T1/2 = 9.3 days in Ag-ve mice. It will be important to measure the in vivo rates for each new metal complex, especially those intended for therapy such as Y-90.