Oncotarget

Research Papers:

Necrosis-targeted combinational theragnostic approach to treat cancer

Yun Ji, Xiaolong Hou, Cuihua Jiang, Wei Liu, Meng Gao, Yue Li, Junhun Wang, Qingqing Wang, Ziping Sun, Xiao Jiang, Nan Yao, Xiaoning Wang, Zhijun Fang, Zhiqi Yin, Jian Zhang _ and Yicheng Ni

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Oncotarget. 2014; 5:2934-2946. https://doi.org/10.18632/oncotarget.1728

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Abstract

Yun Ji1, 2, Cuihua Jiang1, Xueli Zhang1, Wei Liu3, Meng Gao1, Yue Li1, Junhu Wang2, Qingqing Wang1, 2, Ziping Sun4, Xiao Jiang1, Nan Yao1, Xiaoning Wang1, Zhijun Fang1, Zhiqi Yin2, Yicheng Ni1, 4, 5, Jian Zhang1

1 Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China

2 Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R.China

3 Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, P.R.China

4 Radiation Medical Institute, Shandong Academy of Medical Sciences, Jinan 250062, Shandong Province, P.R.China

5 Department of Radiology, Faculty of Medicine, K.U. Leuven, BE 3000, Leuven, Belgium

Correspondence:

Dr. Jian Zhang, e-mail: cpu-yzq@cpu.edu.cn

Dr. Zhiqi Yin, e-mail: chyzq2005@126.com

Keywords: 131-iodine radioiodinated sennidin A (131I-SA), rodent tumor models, combretastatin A4 phosphate (CA4P), diagnosis, necrosis targeting radiotherapy.

Received: December 21, 2013      Accepted: March 08, 2014      Published: March 11, 2014

ABSTRACT

Residual cancer cells and subsequent tumor relapse is an obstacle for curative cancer treatment. Tumor necrosis therapy (TNT) has recently been developed to cause residual tumor regression or destruction. Here, we exploited the avidity of the sennidin A (SA) tracer and radioiodinated SA (131I-SA) to necrotic tumors in order to further empower TNT. We showed high uptake and prolonged retention of SA in necrotic tumors and a quick clearance in other non-targeted tissues including the liver. On SPECT-CT images, tumor mass appeared persistently as a hotspot. Based on the prominent targetability of 131I-SA to the tumor necrosis, we designed a combinational theragnostic modality. The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) was used to cause massive tumor necrosis, which formed the target of 131I-SA that subsequently killed the residual tumor cells by cross-fire irradiation of beta particles. Consequently, 131I-SA combined with CA4P significantly inhibited tumor growth, extended tumor doubling time and prolonged mean animal survival. In conclusion, 131I-SA in combination with necrosis inducing drugs/therapies may generate synergetic tumoricidal effects on solid malignancies by means of primary debulking and secondary cleansing process.


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