Necrosis targeted radiotherapy with iodine-131-labeled hypericin to improve anticancer efficacy of vascular disrupting treatment in rabbit VX2 tumor models
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Haibo Shao1, Jian Zhang2, Ziping Sun3, Feng Chen4, Xu Dai1, Yaming Li1, Yicheng Ni1,2,3,4 and Ke Xu1
1 Department of Radiology, The First Hospital of China Medical University, Shenyang, China
2 Laboratory of Translational Medicine, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, China
3 Radiation Medical Institute, Shandong Academy of Medical Sciences, Jinan, China
4 Department of Imaging & Pathology, Theragnostic Laboratory, University of Leuven, Leuven, Belgium
Ke Xu, email:
Yicheng Ni, email:
Keywords: necrosis, targeted radiotherapy, hypericin, vascular disrupting treatment
Received: June 20, 2014 Accepted: March 03, 2015 Published: March 29, 2015
A viable rim of tumor cells surrounding central necrosis always exists and leads to tumor recurrence after vascular disrupting treatment (VDT). A novel necrosis targeted radiotherapy (NTRT) using iodine-131-labeled hypericin (131I-Hyp) was specifically designed to treat viable tumor rim and improve tumor control after VDT in rabbit models of multifocal VX2 tumors. NTRT was administered 24 hours after VDT. Tumor growth was significantly slowed down by NTRT with a smaller tumor volume and a prolonged tumor doubling time (14.4 vs. 5.7 days), as followed by in vivo magnetic resonance imaging over 12 days. The viable tumor rims were well inhibited in NTRT group compared with single VDT control group, as showed on tumor cross sections at day 12 (1 vs. 3.7 in area). High targetability of 131I-Hyp to tumor necrosis was demonstrated by in vivo SPECT as high uptake in tumor regions lasting over 9 days with 4.26 to 98 times higher radioactivity for necrosis versus the viable tumor and other organs by gamma counting, and with ratios of 7.7–11.7 and 10.5–13.7 for necrosis over peri-tumor tissue by autoradiography and fluorescence microscopy, respectively. In conclusion, NTRT improved the anticancer efficacy of VDT in rabbits with VX2 tumors.
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