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SPECT imaging of interleukin-6 receptor in ovarian tumor xenografts with a novel radiotracer of 99mTc-HYNIC-Aca-LSLITRL

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Abstract

Growing evidences have shown that the IL-6/IL-6R signal pathway promotes the tumor growth, angiogenesis, invasion and migration in various cancers, especially for epithelial ovarian cancer. Hence, including anti-IL-6 antibody (Siltuximab) and anti-IL-6R antibody (Tocilizumab), more and more therapeutic drugs targeting IL-6/IL-6R pathway were developed to block their activity. The molecular imaging of IL-6R is a significant factor for predicting tumor response to IL-6/IL-6R targeted drugs. However, few probes targeting IL-6R were designed and used for the specific detection. The purpose of this study was to develop and evaluate a novel radiotracer, 99mTc-HYNIC-Aca-LSLITRL, for SPECT imaging of interleukin-6 receptor. The expression of IL-6R was determined by western blot, immunofluorescence and immunohistochemistry. HYNIC-Aca-LSLITRL and HYNIC-Aca-TLQASIL were synthesized, and then were labeled with 99mTc. The stability and the cell-binding assay were performed. Ovarian tumor xenografts were established and subjected to SPECT imaging after injection of these two radiopharmaceuticals with or without excess primary peptides. The biodistribution of these two radiotracers was performed in nude mice bearing C13K tumors. 99mTc-HYNIC-Aca-LSLITRL and 99mTc-HYNIC-Aca-TLQASIL were obtained in >95 % labeling yield with favorably stability. In vitro studies demonstrated that the interleukin-6 receptor was overexpressed in ovarian cancer C13K cells. The SPECT imaging of interleukin-6 receptor and biodistribution studies showed that 99mTc-HYNIC-Aca-LSLITRL had higher tumor uptake and significantly lower kidney accumulation compared to 99mTc-HYNIC-Aca-TLQASIL. 99mTc-HYNIC-Aca-LSLITRL could be a promising agent for SPECT imaging of interleukin-6 receptor of ovarian cancer especially for those anti-IL-6R drugs under clinical trials, such as tocilizumab.

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Acknowledgments

We acknowledge the staff of the Department of Nuclear Medicine in Union Hospital of Huazhong University of Science and Technology for providing the Radio-immune Gamma Counter. This work was supported by the National Nature and Science Foundations of China (81172468; 81302249; 81202061, 81271600). Fei Li and Zhenzhong Zhang contributed equally to this manuscript.

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  1. Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People’s Republic of China

    Fei Li, Zhenzhong Zhang, Teng Cheng, Rui Wei, Yun Dai, Mengqin Lv, Danfeng Luo, Ding Ma, Ling Xi & Xiangyi Ma

  2. Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People’s Republic of China

    Xiaohua Zhu & Qingjian Dong

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  1. Fei Li
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Correspondence to Qingjian Dong or Xiangyi Ma.

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All animal experiments were approved by the Hubei Institute Animal Research Committee. All animal experiments were carried out in accordance with the Guide for the Care and Use of Laboratory Animals of Tongji medical college of HUST.

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Li, F., Zhang, Z., Cheng, T. et al. SPECT imaging of interleukin-6 receptor in ovarian tumor xenografts with a novel radiotracer of 99mTc-HYNIC-Aca-LSLITRL. Amino Acids 48, 91–101 (2016). https://doi.org/10.1007/s00726-015-2060-8

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