^125I粒子不同分布组织间植入对荷人胃癌裸鼠移植瘤疗效的影响

Impact of different dose distribution of ^125I seeds interstitial brachytherapy on the effects in human gastric carcinoma bearing nude mice

目的探讨^125I粒子总活度相同时，不同分布的组织间植入对荷人胃癌裸鼠移植瘤疗效的影响。方法建立人胃低分化腺癌BGC-823细胞裸鼠皮下移植瘤模型32只，按随机数字表法分为实验组和对照组。实验组植入总活度33．30MBq ^125I粒子，按照植入单枚活度及分布不同分为高活度组（33．30MBq×1枚）、中活度组（16．65MBq×2枚）、低活度组（11．10MBq×3枚）；对照组植入空源粒子。每组8只裸鼠模型。比较实验和对照组及^125I粒子不同分布状态下对移植瘤体积的抑制率、组织病理学改变、局部皮肤反应、裸鼠体质量和存活率。采用方差分析和秩和检验对数据进行统计学处理。结果各组存活率均为100％。^125I粒子植入第30天裸鼠体质量各组比较，差异无统计学意义[高、中、低活度及对照组分别为（26．44±1．07）、（26．58±0．51）、（27．15±1．37）和（26．92±0．60）g，F=2．23，P〉0．05]。第30天各实验组^125I粒子对肿瘤体积抑制率分别为92．47％，97．15％和89．01％；平均体积各实验组[高、中、低活度组分别为（138．85±16．45）、（52．52±30．54）、（202．72±126．97）mm^3]与对照组[（1843．99±447．63）mm^3]比较，差异均有统计学意义（t值分别为3．092，3．376，3．269，P均〈0．05），中活度组和低活度组组间比较差异有统计学意义（t：2．308，P〈0．05），高活度组分别和中活度组、低活度组组间比较差异均无统计学意义（t值分别为1．300，1．007，P均〉0．05）。高活度组与中活度组组织病理学分级按直肠癌消退分级标准（RCRG）均为RCRG1级；低活度组3只为RCRG3级，4只为RCRG2级，1只为RCRG1级。中、低活度组均未出现放射性损伤，高活度组中4只裸鼠于^125I粒子植入后9～12d出现放射治疗肿瘤学组织（RTOG）1～2级放射性损伤。结论^125I粒子植入治疗中单源活度的选择和分布方式可直接影响疗效和放射性损伤的程度。

Objective 125I seeds interstitiaI brachytherapy has been clinically used for years. However, how the dose distribution affects the therapeutic response remains to be elucidated. The present study was undertaken to investigate the impact of different dose distribution on the effects of ^125I seeds interstitial brachytherapy. Methods Thirty-two human gastric carcinoma bearing nude mice were randomly divided into three treated groups and one control group with eight mice in each group. ^125I seeds were implanted in the treated groups with the same total activity （33.30 MBq）. Based on the dose distribution and activity of single seed, the treated groups were classified to high activity group （33.30 MBq × 1 ） , moderate activity group （16.65 MBq × 2 ） and low activity group （11.10 MBq × 3 ）. The control group was implanted radioactivity-free seeds. The evaluation parameters were obtained after 30 d, which included survival rate, body weight, volume inhibitory rate, histological tumor regression and regional skin reaction. Analysis of variance and Kruskal-Wallis H test were used for data statistical analysis. Results All mice survived during the observation period. There was no significant difference of the body weight among the groups after ^125I seeds im- plantation （F = 2. 23, P 〉 0.05 ）. The volume inhibitory rates in high, moderate and low activity groups were 92. 47% , 97. 15% and 89. 01% , respectively. After treatment the average tumor volume was （138.85 ± 16.45） mm^3 in high activity group, （52.52 ±30.54） mm^3 in moderate activity group, （202.72±126.97） mm^3 in low activity group and （1843.99 ± 447.63 ）mm^3 in control group. In all treated groups, the average tumor volume was significantly smaller than that in control group （t = 3. 092, 3. 376, 3. 269, all P 〈 0.05 ）. However, among the treated groups, statistically significant difference in average tumor volume was only found between moderate activity group and low activity group （ t = 2. 308, P 〈 0.05 ）. The pathological complete response rectal cancer regression grade （RCRG） assessment revealed that RCRG 1 was seen in all the tumors in high activity group and moderate activity group, while all tumors showed RCRG 3 response（H = 23. 50, P 〈 0.005 ） in the control group. In low activity group 1/8 tumor was with RCRG 1, 4/8 with RCRG 2 and 3/8 with RCRG 3. Skin radiation injury was found only in 4/8 nude mice in high ac- tivity group with radiation therapy oncology group （RTOG） grade 1 - 2. Conclusion The activity of single ^125I seed and the dose distribution may exert critical impact on the therapeutic effects and radiation injury in ^125I seeds interstitial brachytherapy.