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Pharmacokinetics of Internally Labeled Monoclonal Antibodies as a Gold Standard: Comparison of Biodistribution of ⁷⁵Se-, ¹¹¹In-, and ¹²⁵I-labeled Monoclonal Antibodies in Osteogenic Sarcoma Xenografts in Nude Mice

Department of Radiology and Nuclear Medicine [M. K., K. E., Y. W., T. S., H. S., J. K.] and Orthopedics [T. Y.], Faculty of Medicine and Viral Institute [S. T.], Kyoto University, Kyoto 606, Japan

In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with ⁷⁵Se by incubating [⁷⁵Se]methionine and hybridoma cells. ⁷⁵Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of ¹²⁵I- and ¹¹¹In-labeled antibodies. ⁷⁵Se-, ¹²⁵I- and ¹¹¹In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of ⁷⁵Se- and ¹²⁵I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of ¹¹¹In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with ⁷⁵Se- and ¹¹¹In-labeled antibodies, whereas ¹²⁵I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both ¹¹¹In- and ¹²⁵I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a "gold standard" of biodistribution of monoclonal antibody, high liver uptake of ¹¹¹In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of ¹¹¹In-labeled antibodies if stably coupled conjugates are administered i.v.

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

Received 8/22/88. Revised 12/ 1/88. Accepted 1/ 5/89.

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