Pharmacokinetics in Patients of an Anti-Carcinoembryonic Antigen Antibody Radiolabeled with Indium-Ill Using a Novel Diethylenetriamine Pentaacetic Acid Chelator1

The pharmacokinetics of the Cl 10 anti-carcinoembryonic antigen an tibody radiolabeled with '"In via a novel benzylisothiocyanate derivative of diethylenetriamine pentaacetic acid have been determined in 12 pa tients. The chelator was attached to the protein via a thiourea bond and in such a way that all 5 carboxymethyl arms were presumably able to participate in chelation. Patients with known or suspected colorectal carcinoma received between 5 and 20 mg of the IgG antibody labeled with5 niCi of '"In. Individual organ radioactivity levels werequantitated, and serum and urine samples were analyzed, principally by size exclusion high-performance liquid chromatography (HPLC). Total urinary excre tion averaged 0.18% of the injected dose/h with large patient to patient variation. At early times postadministration (<8 h) the predominant radiolabeled species in urine was free diethylenetriamine pentaacetic acid most probably administered as a small radiocontaminant in the injectate. Thereafter, radioactivity in urine was primarily present as a low molecular weight catabolic product. Analysis of serum by size exclusion HPLC occasionally showed 3 radioactivity peaks, 2 of which are due to circu lating immune complexes and labeled antibody. The third peak is of low molecular weight and is due to one or more products of antibody catabolism. Transchelation of '"In to circulating transferrin was observed but at modest levels. Quantitation of organ radioactivity showed that 18 ±4 (SI ))'/•; of the injected dose was in the liver at 1 day postadministration and 1.4 ±1.1 and 1.2 ±0.9% was in the spleen and in both kidneys, respectively, at this time. The mean half-life for clearance of total injected radioactivity was fitted to a single exponential and was found to be 34 h (SD, 14 li: .V= M )and that for antibody alone, assessed by size exclusion HPLC analysis of serum samples, was calculated to be 22 h (SD, X li; V = 10). Neither of these values nor organ radioactivity levels were affected by antibody-loading dose.