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Effect of Tumor Mass and Antigenic Nature on the Biodistribution of Labeled Monoclonal Antibodies in Mice

Department of Nuclear Medicine, Kyoto University Hospital, Shogoin, Sakyo-Ku, Kyoto 606 [Y. W., K. E., M. K., Y. K., T. S., H. S., J. K.], and Department of Biochemistry, School of Medicine, Fukuoka University, Fukuoka 812 [M. K., Y. M.], Japan

The effect of tumor mass and antigenic nature on the biodistribution of ¹¹¹In- and ¹²⁵I-labeled monoclonal antibodies (MoAbs) was studied using F(ab')₂ fragments of three representative anti-tumor MoAbs and SW1116 human colorectal carcinoma grown in nude mice. The 19-9, F33-104 anti-CEA, and 17-1A MoAbs showed specific binding to SW1116 cells. The former two MoAbs recognize circulating CA 19-9 with molecular weights of more than 5,000,000 and CEA of M_r 170,000–180,000, respectively, whereas 17-1A reacts with a nonshedding antigen. Both percentage injected dose per gram tumor and tumor-to-blood ratios were inversely proportional to the tumor mass in nude mice administered ¹¹¹In- and ¹²⁵I-labeled 19-9, but liver uptake increased as tumor size increased. Analysis of serum samples and tumor homogenates demonstrated the presence of a high-molecular-weight species, probably due to the antibody binding to CA 19-9. In the case of ¹¹¹In-labeled anti-CEA MoAb, tumor uptake also decreased and liver uptake increased with tumor size, but this effect was less obvious than that of 19-9. In contrast, tumor and liver uptake of ¹²⁵I-labeled anti-CEA MoAb, ¹¹¹In- and ¹²⁵I-labeled 17-1A and control antibodies were independent of tumor mass. The absolute tumor uptake and tumor-to-blood ratios of all ¹²⁵I-labeled antibodies were lower than those of the ¹¹¹In-labeled ones. And the effect of tumor mass was also weaker with ¹²⁵I-labeled antibodies, probably due to in vivo dehalogenation. These results indicate that the effect of tumor size on the incorporation of labeled MoAb into tumors is dependent on the antigenic nature to be targeted and/or radionuclides used for labeling and that high concentrations of circulating high molecular weight antigens may limit in vivo use of MoAb conjugates.

¹ To whom requests for reprints should be addressed, at Department of Nuclear Medicine, Kyoto University Hospital, Shogoin, Sakyo-ku, Kyoto 606, Japan.

Received 8/ 8/88. Revised 1/18/89. Accepted 2/21/89.