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Intratumoral Distribution of Radiolabeled Antibody and Radioimmunotherapy in Experimental Liver Metastases Model of Nude Mouse

Department of Nuclear Medicine and Diagnostic Imaging, Kyoto University, Kyoto
First Department of Molecular Biology, Fukuoka University, Fukuoka, Japan

Correspondence: For correspondence or reprints contact: Noriko Sato, MD, Department of Nuclear Medicine and Diagnostic Imaging, Faculty of Medicine, Kyoto University, 54 Kawahara, Shogoin, Sakyo, Kyoto 606-8507, Japan.

ABSTRACT

The biodistribution and intratumoral distribution of radiolabeled anticarcinoembryonic antigen (CEA) monoclonal antibody in experimental liver metastases and the therapeutic effect of ¹³¹I-labeled anti-CEA antibody on the metastases were studied. Methods: Three weeks after an intrasplenic injection of human colon cancer cells, mice received an intravenous injection of ¹²⁵I- or ¹¹¹In-labeled anti-CEA antibody F33-104. The biodistribution and tumor penetration of radiolabeled antibody were examined by using quantitative autoradiography. To evaluate the therapeutic effect, 5.55, 9.25 or 11.1 MBq (150, 250 or 300 µCi) ¹³¹I-labeled F33-104 were injected into groups of mice that had micrometastases smaller than 1 mm. Control groups were injected with phosphate-buffered saline or ¹³¹I-labeled control antibody. Mice were killed 3 wk later to determinethe size of liver metastases. Results: ¹²⁵I-labeled F33-104 showed a high accumulation in the liver metastases (percentage of injected dose per gram of metastases [%ID/g] >24%, metastasis-to-liver ratio >9.8, metastasis-to-blood ratio >2.1); however, its accumulation was heterogeneous or peripheral in the nodules more than 1mm in diameter. When the antibody dose was increased, antibody penetration was improved, but tumor uptake of radioactivity and specificity ratios decreased. In mice with large metastases, radioactivity in the normal tissue was lower than that in mice with small metastases, resulting in higher metastasis-to-background ratios. ¹¹¹In-labeled antibody showed even higher tumor uptake than ¹²⁵I-labeled antibody (>51 %ID/g). Metastases formation was suppressed in a dose-dependent manner by ¹³¹I-labeled F33-104 injection (5 of 8 mice had no macroscopic tumor after an injection of 5.55 MBq (150 µCi), and all mice had no visible metastasis after an injection of 9.25 or 11.1 MBq [250 or 300 µCi]), whereas tumor progression was seen in the control groups. Conclusion: Liver metastases had easy accessibility to the antibody. Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral distribution of injected antibody and were successfully treated with ¹³¹I-labeled antibody. Very high uptake and satisfactory metastasis-to-liver ratios with ¹¹¹In-labeled antibody suggest that the use of a radiometal with high ß-energy, such as ⁹⁰Y or ¹⁸⁶Re, is preferable for the successful radioimmunotherapy of metastases larger than 1 mm.

Key Words: radioimmunotherapy • antibody • liver metastasis • colon cancer • biodistribution

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