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Treatment of Small-Cell Lung Cancer Xenografts with Iodine-131-Anti-Neural Cell Adhesion Molecule Monoclonal Antibody and Evaluation of Absorbed Dose in Tissue

Department of Nuclear Medicine, Kyoto University Faculty of Medicine, Kyoto
Department of Nuclear Medicine, Gunma University School of Medicine, Gunma
Department of Radiology, Osaka City University School of Medicine, Osaka
Laboratory of Chemotherapy, Aichi Cancer Center, Aichi, Japan

Correspondence: For correspondence and reprints contact: Makoto Hosono, MD, Dept. of Nuclear Medicine, Kyoto University Hospital, Shogoin, Sakyo-ku, Kyoto 606-01, Japan.

ABSTRACT

Human small-cell lung cancer (SCLC) is considered a feasible target for immunotherapy using a radiolabeled monoclonal antibody (Mab). A murine Mab, NE150 (IgG1), reacts with the neural cell adhesion molecule, which is identical to cluster 1 antigen of SCLC. Methods: To estimate their therapeutic effects, NE150 and an isotype-matched control Mab were labeled with ¹³¹I and administered intravenously as a single dose into athymic mice inoculated with a NCI-H69 SCLC xenograft. The absorbed dose in organs was also examined based upon a long-term biodistribution study of ¹³¹I-NEI50. Results: Tumors (initial volume 563.4 ± 223.5 mm³) treated with 11.1 MBq (300 µCi) of ¹³¹I-NE150 diminished and became invisible at days 30–33, demonstrating a 60-day mean growth delay to reach a tripled initial volume compared with sham-treated tumors. Cumulative absorbed doses were estimated to be 2310, 410, 500, 330, and 790 cGy for the tumor, liver, kidney, spleen and lung, respectively. Conclusion: Iodine-131-NE150 had potent therapeutic effects against SCLC transplants in athymic mice, however, careful assessment of the side effects, improvement of radioiodination and chimerization of the Mab might be necessary to achieve efficient targeting in clinical therapeutic applications.

Key Words: radiolabeled monoclonal antibody • small cell lung cancer xenografts