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Relationship between in Vitro Binding Activity and in Vivo Tumor Accumulation of Radiolabeled Monoclonal Antibodies

Department of Nuclear Medicine, Orthopedic Surgery, and Pediatrics, Faculty of Medicine, and Institutes of Virus Research, Kyoto University, Kyoto, Japan

Correspondence: For reprints contact: Keigo Endo, MD, Dept. of Nuclear Medicine, Faculty of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto 606, Japan.

ABSTRACT

The relationship between in vitro cell binding and in vivo tumor accumulation of radiolabeled antibodies was studied using ¹²⁵I and ¹¹¹In-labeled monoclonal antibodies to human osteosarcoma, and a human osteosarcoma xenograft (KT005) in nude mice. Three monoclonal antibodies—OST6, OST7,and OST15—raised against human osteosarcoma recognize the same antigen molecule. Although the binding of both ¹²⁵I- and ¹¹¹In-labeled OST6 to KT005 cells was higher than that of radiolabeled OST7 in vitro, ¹²⁵I-labeled OST6 showed a faster clearance from the circulation and a lower accumulation in the transplanted tumor than ¹²⁵I-labeled OST7. In contrast to the radioiodinated antibodies, the in vivo tumor accumulation of ¹¹¹In-labeled OST6 was higher, although not significantly, than that of ¹¹¹In- labeled OST7. OST15 showed the lowest binding in vitro, and its in vivo tumor localization was also lower than the others. The discrepancy in tumor uptake between OST6 and OST7 labeled with either ¹²⁵I or ¹¹¹In may have been a result of differing blood clearance. These results suggest that binding studies can be used to exclude from in vivo use those antibodies which show very poor binding in vitro, while in vivo serum clearance may be a better test for choosing antibodies with similar binding.

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