Studies on the hepatic uptake of In-111 labeled monoclonal antibodies and the method to reduce the hepatic uptake

Prolonged retention of In-111 labeled monoclonal antibody (In-111 MoAb) in the liver poses problems in radioimmunoscintigraphy. Therefore, subcellular kinetics of In-111 MoAb was investigated. In a study with In-111 225.28S in normal SD rats, the supernatant was found to be a predominant fraction of In-111 radioactivity (61% at 3 hr), with the activity decreasing with time to 21% at 72 hr; however, activity of the mitochondrial fraction was found to increase from 11% to 44%. High performance liquid chromatography for the supernatant revealed that In-111 activity at the earlier time was mainly eluted with the intact IgG peak, and that the major peak activity was thereafter reduced with associated activity peaks found in smaller moistly fractions. Such a sequential distribution change of In-111 225.28S was not found when labeled with I-125. A study with In-111 ZCE025 in mice bearing human colon cancer revealed that activity of the supernatant fraction decreased with time, but the lysosomal activity increased from 14% to 29%, as found in the experiment using normal rats. In tumors, the subcellular distribution of In-111 radioactivity almost remained unchanged throughout the study. The lysosomal fraction was not a predominant fraction of In-111 radioactivity in tumors. When 4 mg of ferric ion (Fe) was administered 48 hr before the injection of In-111 ZCE025, liver uptake of In-111 decreased as compared with the non-Fe group, but tumor uptake was unchanged. Intrahepatic lysosomal radioactivity was smaller in the Fe group than the non-Fe group. These results indicated the involvement of lysosomes in hepatic retention of In-111 MoAb. Once taken up by the liver, the MoAb was metabolized in the supernatant and In-111 ion was transchelated from DTPA onto the lysosomal substances resulting in prolonged retention in the liver. The lysosome in the liver could be saturated by Fe, resulting in a decrease of hepatic uptake without a decrease of tumor uptake. (N.K.) 53 refs