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Department of Radiology, Osaka City University School of Medicine, Osaka
Department of Nuclear Medicine, Kyoto University Faculty of Medicine, Kyoto
Department of Nuclear Medicine, Gunma University Faculty of Medicine, Maebashi and Laboratory of Chemotherapy, Aichi Cancer Center, Nagoya, Japan
Correspondence: For correspondence and reprints contact: Masako N. Hosono, MD, Department of Radiology, Osaka City University Hospital, Asahi-machi, Abeno-ku, Osaka 545, Japan.
ABSTRACT
This study was performed to examine the effect of hyperthermia on the intratumor accumulation of a monoclonal antibody (Mab) in an animal model. Mab NE15O (IgG1) recognizes the neural cell adhesion molecule (NCAM) expressed by human small-cell lung cancer (SCLC) cells. Methods: Athymic mice inoculated with NCI-H69, an SCLC cell line, received an intravenous injection of 125I- and 111In-NE150 and the serial changes of the biodistribution were determined. Furthermore, athymic mice beating NCI-H69 were either Sham-treated or treated by a single hyperthermia at 42°C or 43°C for 1 hr, with the tumor-bearing leg in a water bath using pentobarbital anesthesia. Immediately after heating, the mice were given an intravenous injection of radiolabeled NE150, and the biodistribution was examined at 24 and 48 hr. Results: NE150 localized well in the transplanted tumor when compared with a control Mab. In mice treated at 43°C, there was a 1.34- to 1.67-fold increase in the tumor uptake of 125I- and 111In-NE150 compared to sham-treated mice at both 24 and 48 hr. In addition, a 1.84- to 2.22-fold increase of the tumor-to-blood ratio was demonstrated, since radiolabeled NE150 cleared faster from the circulation in the mice given hyperthermia. A histological study demonstrated the infiltration of neutrophils in the perivascular spaces, indicating an increase of tumor vascular permeability, which might be one of the main reasons for the enhancement of Mab uptake. Conclusion: Hyperthermia seems to be a potential method of achieving an increased tumor accumulation of Mab in the radioimmunotargeting of SCLC.
Key Words: hyperthermia monoclonal antibody human small cell lung cancer xenograft neural cell adhesion molecule
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