HUMAN-IGM MONOCLONAL ANTIBODY-16.88 - PHARMACOKINETICS AND IMMUNOGENICITY IN COLORECTAL-CANCER PATIENTS

Twenty colorectal cancer patients were given an intravenous injection of human IgM monoclonal antibody (MAb) 16.88 (8 mg) conjugated to I-131 for tumor localization. After a 2-week interval, a second injection with 200, 500, or 1000 mg of unlabeled antibody added was given to groups of five patients each. At the end of the 2-hour infusion, 66% of the radioactivity remained in the circulation. Blood clearance of the I-131-labeled MAb 16.88 was biphasic with a mean half-life (T1/2-alpha) of 12 hours and T1/2-beta of 45 hours. Clearance rate was 0.09 L/hour. More than 90% of the I-131 in serum was protein bound, with an immunoreactive fraction of 80% in the first 48 hours. Size exclusion chromatography indicated no degradation products other than I-131 in serum and urine. The urinary excretion rate of I-131 increased to 1.5% of the dose per hour at 24 hours, with 50% of the dose excreted in 34 hours. The pharmacokinetic profile of I-131-labeled MAb 16.88 was neither influenced by the total protein dose of antibody administered nor affected by specific uptake in tumor tissue in individual patients, as determined on early immunoscintigrams. The larger antibody doses showed a slightly slower excretion of I-131. The assays applied to determine immunogenicity were enzyme-linked immunosorbent assay, radioimmunoassay, and the dot-blot assay. They had sensitivities ranging from 5 ng/mL to 0.5-mu-g/mL for goat or rabbit antihuman IgM. The assays did not reveal antihuman antibody responses.