Subcellular kinetics of In-111 monoclonal antibody in liver

Prolonged retention of In-lll monoclonal antibody (MoAb) in the liver poses a limitation in radioimmunoscitigraphy. This study attempted to explore its mechanism by investigating the subcellular kinetics of the In-lll 225.28S, an antimelanoma IgG2a. Forty μCi/l0 μg of the In-lll MoAb was injected iv to SD rats. Liver tissues were sequentially homogenized, and fractionated by 3-step (ultra-)centrifugation. Indium-lll radioactivity was predominant in the supernatant fraction, with decreasing with time (61% at 3 hr to 21% at 72 hr). In contrast, activity in the mitochondrial fraction containing lysosomes increased from 11% to 44%. The nuclear and microsomal radioactivities were relatively constant throughout the study. A similar investigation with I-125 MoAb revealed constant subcellular distribution, but not sequential changes as observed in the case of In-lll MoAb. These results suggest that In-lll MoAb is retained in the lysosomes, once taken up by the hepatic cells, resulting in the prolonged retention of In-lll MoAb in the liver. (Namekawa, K)