中子俘获剂RGD-PEI-AON-(^(157)Gd-DTPA)n治疗荷人甲状腺未分化癌裸鼠模型的研究  

Experimental study of neutron captor agent RGD-PEI-AON-(^(157)Gd-DTPA)n for the treatment of nude mice model with anaplastic thyroid cancer

作　　者：王舰[1] 权友琼[1] 章步程 李俊江 高美佳 楼岑[1] WANG Jian;QUAN Youqiong;ZHANG Bucheng(Department of Nuclear Medicine,Sir Run Run Shaw Hospital Affiliated to School of Medicine,Zhejiang University,Hangzhou 310016,China)

机构地区：[1]浙江大学医学院附属邵逸夫医院核医学科,浙江杭州310016

出　　处：《全科医学临床与教育》2022年第1期8-10,14,共4页Clinical Education of General Practice

基　　金：浙江省自然科学基金(LY19H180005);浙江省医药卫生科技计划项目(2018ZD022)。

摘　　要：目的探讨中子俘获剂RGD-PEI-AON-(^(157)Gd-DTPA)n治疗荷人甲状腺未分化癌(ATC)裸鼠模型的实验研究。方法选择27只SPF级小鼠,移植肿瘤细胞ATC癌细胞株,并随机分为俘获剂组、γ射线组及未照射组三个组,每组9只。通过放射免疫显像仪器SPECT/CT,画取全鼠、瘤体和除瘤体外全鼠的感兴趣区,计算瘤体与周围不同组织的靶/非靶摄取比值(T/N)。后处死小鼠,制作肿瘤组织标本,测量治疗前后肿瘤瘤体长径及瘤体体积变化,计算俘获剂组、γ射线组及未照射组的肿瘤抑制率;并观察俘获剂组治疗后肿瘤局部皮肤及病理学变化情况。结果 ATC瘤体与非瘤体组织的T/N比值在注入后第1、2、3、5、7天逐渐升高,说明俘获剂在正常组织中并没有较高的特异性吸收;俘获剂组及γ射线组在治疗7 d后瘤体长径及瘤体体积较未照射组明显缩小,差异均有统计学意义(t分别=18.39、17.21、15.18、14.32,P均<0.05)。治疗后7 d,俘获剂组肿瘤抑制率高于γ射线组,差异有统计学意义(t=10.21,P<0.05)。7 d内俘获剂组小鼠肿瘤局部皮肤未出现明显红、热等炎症相关反应。病理级电镜检查示:肿瘤细胞破坏严重,可见大片凝固样坏死区,伴有少数凋亡细胞;肿瘤细胞核染色质固缩、碎裂,并存在凋亡小体。结论中子俘获剂RGD-PEI-AON-(^(157)Gd-DTPA)n可以对ATC肿瘤细胞的线粒体、内质网、核酸等造成损伤,抑制其代谢,导致肿瘤细胞凋亡直至死亡。中子俘获剂RGD-PEI-AON-(^(157)Gd-DTPA)n治疗ATC安全、有效,未见明显副作用。Objective To investigate the experimental study of the neutron capture agent RGD-PEI-AON-(^(157)Gd-DTPA)n for the treatment of nude mice model with anaplastic thyroid cancer(ATC). Methods Twenty-seven SPFgrade mice were selected to transplant tumor cells into ATC cancer cell lines,and were randomly divided into three groups:capture agent group,γ ray group and unirradiated group,9 in each group.Through the radioimmunography instrument SPECT/CT,the area of interest of whole mouse,tumor body and whole mouse except tumor body was drawn,and the target to nontarget ratio(T/N)of tumor body to different surrounding tissues was calculated.After execution,mice were executed,tumor tissue samples were made,tumor body length and tumor volume changes were measured before and after treatment,and the tumor inhibition rates of the capture agent group,γ ray group and unirradiated group were calculated.The local skin and pathological changes of tumors were observed after treatment in the capture agent group. Results The T/N ratio of ATC tumor body to non-tumor tissue gradually increased after 1,2,3,5,7 days injection,indicating that the capture agent did not have high specific absorption in normal tissues.Compared with the unir-radiated group,the tumor length and volume of the capture agent group and the γ ray group decreased significantly,the differences were statistically significant(t=18.39,17.21,15.18,14.32,P<0.05). Seven days after injection,the tumor inhibition rate of the capture agent group was higher than that of the γ ray group(t=10.21,P<0.05).There were no obvious red,heat and other inflammatory related reactions on the local skin of the tumors of mice in the capture agent group within 7 days.Pathological-level electron microscopy showed that the tumor cells were seriously damaged,and large areas of coagulation-like necrosis were visible,accompanied by a few apoptotic cells,the chromatin of tumor cells solidified and fragmented,and there were apoptotic corpuscles. Conclusion The capture agent RGD-PEI-AON-(^(157)Gd-DT

关 键 词：中子俘获剂 合成 甲状腺未分化癌 

分 类 号：R-332[医药卫生] R736.1