Gao Long, Zhang Jian, Ma Tengchuang, Yao Nan, Gao Meng, Shan Xin, Ni Yicheng, Shao Haibo, Xu Ke
Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Laboratory of Translational Medicine, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, China.
Oncotarget. 2016 Aug 9;7(32):51450-51461. doi: 10.18632/oncotarget.9848.
Residual tumor resulting in tumor recurrence after various anticancer therapies is an unmet challenge in current clinical oncology. This study aimed to investigate the hypothesis that radioiodinated hypericin (131I-Hyp) may inhibit residual tumor recurrence after microwave ablation (MWA) on rat orthotopic liver allograft sarcoma models.Thirty Sprague-Dawley (SD) rats with hepatic tumors were divided into three groups: Group A received laparotomy MWA and sequential intravenous injection (i.v.) of 131I labelled hypericin (131I-Hyp) in a time interval of 24 h; Group B received only laparotomy MWA; Group C was a blank control. Tumor inhibitory effects were monitored with in vivo magnetic resonance imaging (MRI) and these findings were compared to histopathology data before (baseline, day 0) and 1, 4, and 8 days after MWA. In addition, biodistribution of 131I-Hyp was assessed with in vivo single-photon emission computed tomography-computed tomography (SPECT-CT) imaging, in vitro autoradiography, fluorescent microscopy, and gamma counting.A fast clearance of 131I-Hyp and increasing deposit in necrotic tumors appeared over time, with a significantly higher radioactivity than other organs (0.9169 ± 1.1138 % ID/g, P < 0.01) on day 9. Tumor growth was significantly slowed down in group A compared to group B and C according to MRI images and corresponding tumor doubling time (12.13 ± 1.99, 4.09 ± 0.97, 3.36 ± 0.72 days respectively). The crescent tagerability of 131I-Hyp to necrosis was visualized consistently by autoradiography and fluorescence microscopy.In conclusion, 131I-Hyp induced necrosis targeted radiotherapy improved therapeutic outcomes of MWA on rat orthotopic liver allograft sarcoma models.
在当前临床肿瘤学中,各种抗癌治疗后残留肿瘤导致肿瘤复发是一个尚未解决的挑战。本研究旨在探讨放射性碘化金丝桃素(131I-Hyp)可能抑制大鼠原位肝移植肉瘤模型微波消融(MWA)后残留肿瘤复发的假说。30只患有肝肿瘤的Sprague-Dawley(SD)大鼠被分为三组:A组接受剖腹MWA,并在24小时间隔内序贯静脉注射(i.v.)131I标记的金丝桃素(131I-Hyp);B组仅接受剖腹MWA;C组为空白对照。用体内磁共振成像(MRI)监测肿瘤抑制作用,并将这些结果与MWA前(基线,第0天)以及MWA后1、4和8天的组织病理学数据进行比较。此外,用体内单光子发射计算机断层扫描-计算机断层扫描(SPECT-CT)成像、体外放射自显影、荧光显微镜检查和γ计数评估131I-Hyp的生物分布。随着时间的推移,131I-Hyp快速清除,坏死肿瘤中的沉积增加,在第9天放射性明显高于其他器官(0.9169±1.1138%ID/g,P<0.01)。根据MRI图像和相应的肿瘤倍增时间(分别为12.13±1.99、4.09±0.97、3.36±0.72天),A组的肿瘤生长与B组和C组相比明显减慢。放射自显影和荧光显微镜检查一致显示131I-Hyp对坏死的新月形靶向性。总之,131I-Hyp诱导的坏死靶向放疗改善了大鼠原位肝移植肉瘤模型中MWA的治疗效果。