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Abstract
Lanatoside C has a promising anti-tumor activity and is a potential candidate for radiosensitizers. In this study, we have investigated the therapeutic efficacy of the combination of 131I-trastuzumab and lanatoside C for inhibition of human epidermal growth factor receptor 2 (HER2) positive tumor progression in NCI-N87 xenograft model. The combination treatment (131I-trastuzumab and lanatoside C) showed highest cytotoxicity when compared to non-treated control or trastuzumab alone or 131I alone or 131I-trastuzumab alone in vitro. Biodistribution studies using 131I-trastuzumab or combination of 131I-trastuzumab and lanatoside C showed tumor uptake in BALB/c nude mice bearing HER2 positive NCI-N87 tumor xenograft model. The higher tumor uptake was observed in 131I-trastuzumab (19.40 ± 0.04% ID/g) than in the combination of 131I-trastuzumab and lanatoside C (14.02 ± 0.02% ID/g) at 24 h post-injection. Most importantly, an antitumor effect was observed in mice that received the combination of 131I-trastuzumab and lanatoside C (p = 0.009) when compared to control. In addition, mice received lanatoside C alone (p = 0.085) or 131I-trastuzumab alone (p = 0.160) did not significantly inhibit tumor progression compared with control. Taken together, our data suggest that combination of 131I-trastuzumab and lanatoside C might be a potential synergistic treatment for radioimmunotherapy to control the HER2 positive tumor.

Affiliations

Nagarajan Vinod #  1 , Jae Hyung Kim #  2 , Seungbum Choi  2 , Ilhan Lim  3   4   5
1 Department of Nuclear Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, (KIRAMS), Seoul, 01812, Republic of Korea.
2 Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, (KIRAMS), Seoul, 01812, Republic of Korea.
3 Department of Nuclear Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, (KIRAMS), Seoul, 01812, Republic of Korea. ilhan@kirams.re.kr.
4 Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, (KIRAMS), Seoul, 01812, Republic of Korea. ilhan@kirams.re.kr.
5 Department of Radiological & Medico-Oncological Sciences, University of Science and Technology (UST), Seoul, 01812, Republic of Korea. ilhan@kirams.re.kr.
# Contributed equally.