不同浓度^(131)I-ELP近距离放射治疗兔VX2肝癌模型的实验研究  

Brachytherapy using elastin-like polypeptide with different concentrations of ^(131)I for treatment of VX2 liver tumor in rabbits

作　　者：李茜 刘欣培 王多伟 申一鸣[4] 贾强[4] 刘文天[1] Qian Li;Xin-Pei Liu;Duo-Wei Wang;Yi-Ming Shen;Qiang Jia;Wen-Tian Liu(Department of Gastroenterology,Tianjin Medical University General Hospital,Tianjin 300052,China;Department of Gastroenterology,the Fifth Central Hospital of Tianjin,Tianjin 300450,China;Department of General Surgery,Tianjin Medical University General Hospital,Tianjin 300052,China;Department of Nuclear Medicine,Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院消化科,天津市300052 [2]天津市第五中心医院消化科,天津市300450 [3]天津医科大学总医院普外科,天津市300052 [4]天津医科大学总医院核医学科,天津市300052

出　　处：《世界华人消化杂志》2019年第8期485-493,共9页World Chinese Journal of Digestology

基　　金：天津市科委慢性病防治科技重大专项;No.17ZXMFSY00210;天津市卫计委卫生行业重点攻关项目;No.15KG149~~

摘　　要：背景近距离放射治疗是治疗癌症的靶向放射疗法,类弹性蛋白多肽(elastin-like peptide, ELP)是一种人工合成的弹性蛋白,其具有的自组装性、温度响应性和非免疫原性等独特优势,为其成为放射性核素^(131)I的载体提供了可能.目的制备放射性核素^(131)I标记的ELP,研究不同放射性浓度^(131)I-ELP对兔VX2肝癌模型近距离放射治疗的有效性及差异性,为其临床应用提供依据.方法应用Iodogen法对ELP进行^(131)I碘化标记,制备100 mCi/mL和50 mCi/mL放射浓度的^(131)I-ELP;在B超引导下将不同浓度^(131)I-ELP药物及ELP溶液随机注入15只VX2模型兔的肝肿瘤内进行近距离放射性治疗及空白对照观察,以注入100 m Ci/mL ^(131)I-ELP为高放射浓度治疗组(H组, n=5);注入50 mCi/mL ^(131)I-ELP为低放射浓度治疗组(L组, n=5)及注入ELP溶液为空白对照组(C组, n=5).治疗后,定期行B超及血液学检查以观察治疗效果,治疗组行单光子发射计算机断层扫描/计算机断层扫描(single-photon emission computed tomography/computedtomography,SPECT/CT)检查,观察三组动物的自然生存时间和病理学检查.结果 H组的动物生存期最长(61.4d±10.50d),L组的动物生存期为(52.6 d±8.85 d), C组的动物生存期最短(39.2d±5.63d),三组之间有显著差异(P <0.05).治疗后7 d、14 d, SPECT/CT示治疗组的放射性持续位于肿瘤内部.H和L组的肿瘤生长率显著低于C组(P <0.05).H和L组治疗后7 d、14 d肝功能指标丙氨酸氨基转移酶(alanine aminotransferase, ALT)和天冬氨酸氨基转移酶(aspartate aminotransferase, AST)显著低于C组(P<0.05),治疗后7 d L组的ALT水平显著低于H组(P <0.05);治疗后14d,L组AST数值显著低于H组(P <0.05),提示H组的肝功能受损更严重.治疗后7 d、14 d三组Hb、RBC计数无显著差异.病理组织学检查示H组癌旁正常肝组织存在小叶中央静脉淤血、肝窦及汇管区小胆管扩张、肝内纤维增生,在肿瘤组织内发现大片状坏BACKGROUND Brachytherapy is a targeted radiation therapy for cancer.The elastin-like peptide(ELP)is a genetically engineered peptide that has unique advantages such as self-assembly,temperature responsiveness,and nonimmunogenicity,which make it possible to become the carrier of the radionuclide 131I.AIM To evaluate the effectiveness of brachytherapy in a rabbit model of VX2 liver tumor using elastin-like polypeptide as a radionuclide 131I carrier and compare the effectiveness of 131I-ELP at different radioactive concentrations to provide evidence for its clinical application.METHODS ELP as a carrier was labeled with 131I by the iodogen method,and different concentrations of 131I-ELP were prepared.Under ultrasound guidance,different concentrations of 131I-ELP and ELP solution were randomly injected into 15 rabbits with VX2 liver tumor for brachytherapy and blank control observation.The rabbits were divided into the following groups:high-dose radiation group(injection with 100 mCi/mL 131I-ELP;group H,n=5);low-dose radiation group(injection with 50 mCi/mL 131I-ELP;group L,n=5);and blank control group(injection with ELP solution;group C,n=5).Periodic biochemical and sonographic examinations were performed to assess the therapeutic efficacy after treatment.Single-photon emission computed tomography/computed tomography(SPECT/CT)was additionally performed in the treatment groups.The natural survival time of animals in the three groups was determined.In addition,histopathological examination was performed.RESULTS The survival time of animals was the longest in group H(61.4 d±10.50 d)and the shortest(39.2 d±5.63 d)in group C.The survival time of animals in group L was 52.6 d±8.85 d.Significant differences were observed in the survival time among the three groups(P<0.05).At 7 and 14 d after treatment,SPECT/CT showed that 131I-ELP was continuously localized in liver tumors in groups H and L.The tumor growth rates in groups H and L were significantly lower than that in group C(P<0.05).Alanine aminotransferase(ALT)and aspa

关 键 词：肝癌 兔VX2肿瘤模型 ^131I 类弹性蛋白多肽 放射性浓度 

分 类 号：R735.7[医药卫生—肿瘤] R730.55[医药卫生—临床医学] R-332