G.L. De Nardo

Non-dehalogenation mechanisms for excretion of radioiodine after administration of labeled antibodies.

In patients or mice with cancer the pharmacokinetic behavior of radioiodinated and radiometal chelated antibodies has been observed to be different. Rapid clearance from the tissues and excretion into the urine can occur after injection of radioiodinated antibodies. These observations have been interpreted to reflect in vivo dehalogenation of the antibody. This publication describes a variety of other mechanisms that can underlie these phenomena. These mechanisms include receptor uptake and catabolism of antibody and instability of the labeled antibody due to the labeling conditions. Specifically, the relative masses of chloramine-T and antibody in the iodination reaction mixture, the level of iodination of the antibody, and the amount of antibody administered to the recipient are all factors which can influence the clearance of radioiodinated antibody from the recipient. The final determinant for the different behavior of radioiodinated and In-111 metal chelated antibody relate to the different biologic pathways of indium when compared to iodine

Analysis of antiglobulin (HAMA) response in a group of patients with B-lymphocytic malignancies treated with 131I-Lym-1

Host development of human anti-mouse antibodies (HAMA) in response to administered antibodies has been reported as a problem for antibody imaging and therapy. However, radioimmunotherapy has been shown to be effective in patients with B-cell malignancies because their immunodeficient state precludes or delays development of a HAMA response to mouse antibodies. Baseline HAMA activity was assayed in 60 patients with B-lymphocytic non-Hodgkins lymphoma or chronic lymphocytic leukemia and sequentially in 43 patients who were subsequently treated with radiolabeled Lym-1 antibody. Pre-existing “HAMA” activity was found in 3 (5%) of the 60 patients screened for treatment consideration. The incidence of development of HAMA in the 43 patients treated with multiple doses of radiolabeled Lym-1 antibody was 12 (28%). There was no evidence for an anaphylactoid or related response in the HAMA positive patients. HAMA activity interrupted therapy in 14% of the patients (6 of 43) but did not preclude therapeutic responses to radiolabeled Lym-1 therapy. Median survival for the HAMA positive patients was longer (18 months) than for those who did not develop HAMA activity (9 months).