内照射与化疗协同兼具多模态影像监测功能的诊疗剂用于肝脏VX2瘤经动脉介入治疗的研究

As the main treatment for liver tumor that lack of the possibility of excision, clinical effect of transarterial chemoembolization (TACE) should be improved, where the controlled-releasing drugs and chemoradiotherapy may have the promising values. Based on the previous research on dual-modal imaging and sensitized radiotherapy, BaGdF5@CDDP@SiO2(188Re-Sn) was designed and developed as theranostics with the ability of controlled release, chemoradiotherapy, and multimodal imaging monitoring. In this research, rabbits models with VX2 liver tumor were randomly divided and treated via transarterial interventional embolization: control group (normal saline), research group I (iodipin + CDDP), research group II (iodipin + CDDP controlled-releasing drugs), research group III (iodipin + Re-188 labeled Sn colloids), research group IV (iodipin + Re-188 labeled functional particles), and research group V (iodipin + Re-188 labeled & CDDP controlled-releasing drugs). Pathological findings were set as gold standard, and comparisons among groups and between pre- and post-treatments were performed to make a comprehensive evaluation on the advantages of chemoradiotherapy, to explore the influence of therapeutic factors on tumor angiogenesis, hypoxia-inducible factor and cellular apoptosis. Bio-safety of theranostics was evaluated based on the therapeutic effects and blood test results. Overall, this research aims to improve the curative effect of interventional treatment of liver cancer, and provide valuable guide for the clinical translation of multi-functional theranostics.

TACE是不能手术切除肝癌的主要治疗方法，临床疗效亟需提高，其方法包括缓释化疗药物、结合放射治疗等。我们在前期开展双模态成像及放疗增敏研究的基础上，设计集核素内照射与化疗药物缓释协同、多模态影像监测于一体的多功能诊疗剂BaGaF5@CDDP@SiO2(188Re-Sn)。利用兔肝脏VX2瘤模型，分组经导管肝动脉栓塞给药：对照组（生理盐水）、组Ⅰ（碘油+顺铂）、组Ⅱ(碘油+顺铂缓释材料)、组Ⅲ（碘油+Re-188-Sn胶体）、组IV（碘油+Re-188标记功能材料）、组V（碘油+Re-188标记的顺铂缓释材料）。以病理为金标准，通过组间及治疗前后自身比较，综合评价诊疗剂的内照射与缓释化疗药物的协同优势、多模态影像监测的优势，探讨治疗因素对肿瘤新生血管生成、乏氧诱导因子及细胞凋亡的影响；结合血液指标检测结果，评价诊疗剂的生物安全性。为提高肝癌介入治疗效果及多功能诊疗剂的临床转化提供参考。