外照射联合瘤内注射~(131)I-chTNT对荷Lewis瘤小鼠肿瘤的治疗作用

目的 研究外照射联合瘤内注射~(131)I-肿瘤细胞核人鼠嵌合单克隆抗体(chTNT)对荷瘤小鼠肿瘤生长和体内放射性分布的影响.方法 建立C57BL近交系荷Lewis瘤小鼠模型64只,当肿瘤直径达6.0 mm时,用随机数字法分组进行荷瘤小鼠体内分布实验(18只)及~(131)I-chTNT显像(6只),均分为单药组和外照射联合组(小鼠分配9只×2和3只×2),观察给药后1,3和5 d肿瘤组织及血液、对侧大腿肌肉、胃、肝、肾、心、肺的放射性,用每克组织百分注射剂量率(%ID/g)表示;肿瘤生长效应实验设4个组(每组10只):对照组、单药组、外照射组和联合组,观察指标为肿瘤生长延迟时间.采用SPSS 11.5软件,组间比较行t检验.结果 荷瘤小鼠体内分布实验中联合组肿瘤组织放射性在1[(11.95±1.33)%ID/g]和3 d[(9.38±1.25)%ID/g]均高于单药组[(7.86±0.94)和(6.57±0.71)%ID/g],2组间差异有统计学意义(t值分别为4.326,3.555,P均<0.05).2组中正常组织的放射性差异均无统计学意义(t值0.118～1.445,P>0.05).~(131)I-chTNT显像结果 示外照射可增加荷瘤小鼠瘤内~(131)I-chTNT的滞留量,并延长其滞留时间;生长效应实验示:单药组、外照射组的绝对延迟时间分别为(3.3±1.75)和(6.0 4±2.02)d,联合组的绝对延迟时间为(9.5±1.93)d,标准化延迟时间为6.2 d,~(131)I-chTNT对放射治疗的增效因子为1.03.结论 外照射联合瘤内注射~(131)I-chTNT可增加瘤内~(131)I-chTNT的滞留量,并延长其滞留时间,二者联合应用可提高对荷瘤小鼠肿瘤的治疗效果.

The study of irradiation combined with intratumoral injection of ~(131)I-chTNT-for Lewis tumor of C57BL mice

Objective ~(131)I-chTNT is a new targeted radiophamaceutical.The objective of this study was to investigate(1)the seintigraphic biodistribution of this tracer in mice bearing Lewis tumor at different time frames after intratumoral injection of ~(131)I-chTNT combined with or without irradiation,and(2)its therapeutic effects on tumor growth.Methods When the diameter of tumor in C57BL mice bearing Lewis carcinoma in the right leg reached 6.0 mm.the mice were randomly assigned to different groups to receive treatment.The biodistribution (percentage activity of injected dose per gram of tissue,%ID/g)of ~(131)I-chTNT in ~(131)I-chTNT group and ~(131)I-chTNT combined with irradiation group was studied at 1,3,5 d after intratumoral iniection in tumor-bearing mice.The effect oftreatment was assessed by delay of tumorgrowth.Statistical analysis was performed with SPSS 11.5 and t-test was used to compare the data of different group.Resuits The biodistribution data indicated that higher uptake of tumor tissue both in ~(131)I-chTNT group((7.86±0.94) and(6.57±0.71)%ID/g)and in combined group((11.95±1.33)and(9.38±1.25)%ID/g)was at 1 and 3 d post injection(The data of the two groups was compared:t=4.326,3.555,respectively,both P< O.05).Tere were no significant side effects in the combined group.Tumor growth analysis in 40 mice showed that the absolute growth delay for ~(131)I-chTNT group.irradiation group and the combined group was (3.3±1.75),(6.0±2.02)and(9.5±1.93)d respectively.The nominal growth delay was 6.2 d,and the enhancement factor of ~(131)I-chTNT for irradiation was 1.03.Conclusions Irradiation combined with intratumoral injection ~(131)I-chTNT can increase and prolong the uptake of ~(131)I-chTNT in tumors without having greater side effects.The combination therapy can inerease therapeutic efficacy for tumor.bearing C57 mice.