Toxicity of Indium-111 on the Radiolabeled Lymphocyte

The radiolabeling of lymphocytes with 111In has resulted in detectable toxic changes in the cells. The mechanisms of toxicity for lymphocytes have been related to the label's radioactivity and to the chelator used to mediate the intracellular localization. These mechanisms were examined by assessing cellular function with mitogen-mediated blastogenesis after labeling lymphocytes with either the chelator (tropolone) alone, 111In complexed with tropolone, or cadmium (the decay product of 111In) complexed with tropolone. Successful lymphocyte labeling with 111In was shown to be dependent upon the concentration of the chelator (tropolone). Increasing concentrations of tropolone inhibited lymphocyte function to a variable degree. Further reduction in cellular function was detected after incorporation of a constant amount of 111In or 111In's decay product, cadmium. Lymphocyte function was decreased by these two labels in a parallel linear manner. This same toxic effect was seen after labeling with small constant amounts of tropolone and increasing quantities of 111In or cadmium. Thus, although both the required chelator and the radiobiologic exposure have a deleterious effect on the lymphocyte, significant lymphocyte toxicity appears to result from the metal-to-cell interaction as a result of the metal decay product (cadmium).