125Ⅰ放射性粒子治疗胰腺癌早期疗效的动物实验研究

目的 探讨18F-FDG Micro-PET/CT对125Ⅰ粒子组织间植入治疗胰腺癌裸鼠移植瘤疗效进行早期评价的应用价值.方法 人胰腺癌SW1990细胞株接种于BABL/c裸鼠右后肢,2周后成瘤大小8～10 mm.12只荷瘤裸鼠随机分为空白对照组、空载粒子组和125I粒子植入组,每组4只.治疗前及治疗后1周行18F-FDG Micro-PET/CT检查,计算最大标准摄取值(SUVmax)、平均标准摄取值(SUVmean)、肿瘤体积及坏死率.瘤体标本行HE染色和细胞质胸腺嘧啶核苷激酶(TK1)免疫组织化学检查.结果 3组治疗前SUVmax和SUVmean值差异无统计学意义,治疗后1周3组SUVmax和SUVmean分别为3.53±1.20和0.57±0.26、3.83±2.13和0.59±0.24、0.29±0.23和0.02±0.01,差异有统计学意义(F=7.62、10.34,P＜0.01).125Ⅰ粒子植入组SUVmax和SUVmean明显低于空载粒子植入组及空白对照组,且明显低于治疗前.3组治疗前肿瘤坏死率无明显差异,免疫组织化学染色发现,3组TKI阳性染色指数分别为(64.25±1.71)%、(62.25±2.22)%和(38.25±1.71)%,差异有统计学意义(F=233.67,P＜0.01),125Ⅰ粒子植入组明显低于空载粒子植入组及空白对照组.SUVmax与TK1阳性染色指数有一定的正相关性(r=0.85,P＜0.01).结论 18F-FDGMicro-PET/CT是监测125Ⅰ粒子治疗胰腺癌早期疗效的有效方法.

Abstract：

Objective To investigate the application value of early evaluation and monitoring of 125Ⅰ interstitial implantation in a pancreatic cancer xeuograft.Methods Xenograft models were created by subcutaneous injection of Sw 1990 human pancreatic cancer cell suspensions into the right hind limbs of the immunodeficient BABL/c nude mice.The tumors size were about 8-10 mm after two weeks.The mice were randomly divided into 3 groups,including control group (n = 4) ,empty seed implantation group (n = 4)and 125Ⅰ implantation group (n = 4).Before treatment and one week after treatment,18F-FDG Micro-PET/CT scan was performed and then maximum standardized uptake values (SUVmax),mean standardized uptake values (SUVmean),tumor size and necrosis rate were measured.HE staining and TK1 immunohistochemistry examination were carried out in the paraffin-embedded sample.Results Before treatment the SUVmax and SUVmean values of three groups did not reach statistical significance.One week after treatment the SUVmax and SUV values of three groups were 3.53 + 1.20 and 0.57±0.26 vs.3.83±2.13 and0.59 ±0.24vs.0.29±0.23 and0.016±0.001,respectively,with a significant difference (F =7.62,P =0.01 ; F = 10.34,P =0.005).The SUVmax and SUVmean values of 125Ⅰ implant group were significantly lower than empty seed implant group and control group and were significantly lower than before treatment.Before treatment,tumor necrosis rate of three groups were not significantly different.Immunohistochemical staining found the TK1 positive staining index of three groups were respectively (64.25±1.71) % ,(62.25±2.22) % and (38.25±1.71) % with statistically significant difference (F =233.67,P < 0.001).The TK1 positive staining index of 125Ⅰ implant group was significantly lower than empty seed implant group and control group.The SUVmax values had some positive correlation with TK1 positive staining index (r = 0.85,P = 0.001).Conclusions 18F-FDG Micro-PET/CT may be useful as a noninvasive imaging modality to assess early response to 125Ⅰ seed brachytherapy in a pancreatic cancer xenograft.