PHARMACOKINETICS OF THE FO23C5 ANTI-CEA ANTIBODY FRAGMENT LABELED WITH TC-99(M) AND IN-111 - A COMPARISON IN PATIENTS

The FO23C5 anti-carcinoembryonic antigen (CEA) F(ab')2 antibody was radiolabelled with In-111 via diethylenetriaminepentaacetic acid (DTPA) and directly with Tc-99m by stannous ion and mercaptoethanol antibody reduction to compare the pharmacokinetics of these three agents. Four patients received 15 mCi Tc-99m-Fab' 1 week before receiving 1 mCi In-111-F(ab')2. Five additional patients received only the Tc-99m-Fab'. Radiochromatograms by high-performance liquid chromatographic (HPLC) analysis of serum and urine samples from patients receiving In-111 were typical of those observed by us previously in connection with other antibodies. The identical analyses of samples from patients receiving Tc-99m showed no differences with the method of reduction and more complex. radiochromatograms. In addition to peaks due to a mixture of labelled F(ab')2 and Fab' fragments and, occasionally, immune complexes, there were several peaks due to labelled cysteine and other small labelled species present in both serum and urine. The biodistribution of Tc-99m was as expected for a labelled Fab' fragment: relative to In-111, Tc-99m cleared rapidly from circulation and into kidneys and urine. Liver levels of In-111 and Tc-99m were surprisingly similar at 1 day (12 versus 9% ID) although initial In-111 levels were lower and increased while Tc-99m levels were higher and decreased. Spleen levels were also similar. In 4/9 patients receiving Tc-99m, hepatobiliary clearance was observed at levels which could confuse interpretation whereas this mode of clearance was observed in only 1/4 patients receiving In-111. Image quality was superior with In-111 versus Tc-99m at 1 day postadministration as judged by counting rates and background activity whereas the opposite was true at 2-3 h postadministration.