【作者】 王忠敏；

【导师】 刘芬菊；

【作者基本信息】 苏州大学 ， 放射医学， 2011， 博士

【摘要】 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裸鼠右下肢旁腹股沟区偏背侧皮下,成瘤后取瘤块接种,6周后成瘤8-10mm,共12只成瘤大小合适的裸鼠用于实验,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(SUV_max)、平均标准摄取值(SUV_mean)、肿瘤体积及坏死率。瘤体标本行HE染色和TK1免疫组织化学检查。结果:3组治疗前SUV_max和SUV_mean值分别为2.73±2.29和0.58±0.37,2.65±1.36和0.56±0.41,3.63±1.65和0.85±0.51差异无统计学意义,治疗后1周3组SUV_max和SUV_mean分别为3.53±1.120和0.57±0.26,3.83±2.133和0.59±0.236,0.29±0.23和0.02±0.001,差异有统计学意义（F=7.62,P=0.01; F=10.34, P=0.005）。¹²⁵I粒子植入组SUV_max和SUV_mean明显低于空载粒子植入组及空白对照组,而空载粒子组和空白对照组无统计学差异;且¹²⁵I粒子植入组SUV_max和SUV_mean明显低于治疗前,而空载粒子组和空白对照组均较治疗前无统计学差异。3组治疗前肿瘤坏死率分别为（9.75±3.10）%, （11.41±5.33）%和（12.46±4.69）%,无统计学意义;免疫组织化学染色发现,3组TK1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<0.001）,¹²⁵I粒子植入组明显低于空载粒子植入组及空白对照组（P<0.001）,SUV_max与TK1阳性染色指数有一定的正相关性（r=0.85,P=0.001）。结论:¹⁸F-FDG Micro-PET/CT是监测¹²⁵I粒子治疗胰腺癌早期疗效的有效方法。影像引导下¹²⁵I放射性粒子组织间植入治疗胰腺癌疗效评估的临床实验研究目的:探讨CT引导下¹²⁵I放射性粒子组织间植入治疗胰腺癌技术的可行性和临床疗效。方法:2004年12月至2010年6月对40例手术不能切除的晚期胰腺癌患者进行CT引导下植入¹²⁵I粒子治疗。全组40例患者中,男25例,女15例,年龄38-89岁,中位年龄69岁。采用TPS（treatment planning system）重建胰腺肿瘤的三维立体图像,计算出¹²⁵I粒子植入的粒子数目、空间分布和剂量分布率,在CT引导下将¹²⁵I粒子植入胰腺肿瘤内,采用¹²⁵I粒子活度为0.5-0.9mCi/颗,相隔1.0～1.5cm植入,避开血管、胰管等周围重要脏器。放射性粒子的肿瘤匹配周边剂量（matched peripheral dose,MPD）为31.1～130Gy。中位植入粒子36颗（18～68颗）,术后即刻行CT扫描进行粒子质量验证。结果:全组肿瘤平均直径为4.9cm。治疗后随访2～30个月。术后患者顽固性疼痛症状明显缓解（P<0.05）,Karnofsky评分显著提高（P<0.05）。平均术后2～5d疼痛开始缓解。术后2个月CT随访,肿瘤完全缓解（CR）3例,部分缓解（PR）20例,无变化（NC）14例,进展（PD）3例,总有效率为（CR+PR）57.5%。全组中位生存期为10.2个月,Ⅱ、Ⅲ、Ⅳ期粒子植入术后中位生存期分别为14.7、10.9及7.1个月;6个月和12个月累计生存率分别为100%、88%、62%和70%、41%、0%。40例患者中有21例患者术前CA19-9升高,术后1～3个月复查CA19-9降低,¹²⁵I粒子植入后1个月肿瘤标志物水平与植入前比较明显降低（P<0.05）。3例患者术后随访发现4颗粒子迁移到肝脏内。在随访过程中未见上消化道出血、胰腺炎、胰瘘及放射性肠炎等严重并发症。结论:CT引导下¹²⁵I放射性粒子组织间植入治疗胰腺癌,近期疗效确切,具有很好的姑息止痛疗效,能改善患者的生活质量,是一种安全、有效、并发症发生率低的微创治疗方法,远期疗效尚待进一步随访和观察。更多还原

【Abstract】 Early Therapy Monitoring of ¹²⁵I seed interstitial implant in animal studies of Pancreatic Cancer XenograftObjective: ¹²⁵I seed interstitial implant brachytherapy has some clinical effectiveness for pancreatic cancer. In this study, through the use of combined micro-positron emission tomography （PET）/computed tomography （CT）, we investigated potential the application of ¹²⁵I interstitial implant in a pancreatic cancer xenograft for early evaluation and diagnosis.Methods: The human pancreatic cell line SWl990 was subcutaneously injected into right lower limb partial dorsal area next to the groin of the immunodeficient BABL / c nude mouse. Tumors were cut into small pieces after tumor formation, and the tumor pieces were inoculated in nude mice.The tumor size reached 8-10mm after six weeks. The mice were randomly divided into 3 groups, the control group （n=4）, empty seed implant group（n=4） and ¹²⁵I implant group （n=4）. Before treatment and one week after treatment, ¹⁸F-FDG Micro-PET/CT scan was performed and then maximum standardized uptake values (SUV_max), mean standardized uptake values (SUV_mean), 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 SUV_max and SUV_mean values of three groups were respectively 2.73±2.29 and 0.58±0.37 vs.2.65±1.36 and 0.56±0.41 vs. 3.63±1.65 and 0.85±0.51 which showed no statistical significance. At one week after treatment the SUV_max and SUV_mean values of three groups were respectively 3.53±1.20 and 0.57±0.26 vs. 3.83±2.13 and 0.59±0.24 vs. 0.29±0.23 and 0.016±0.001, which had a significant difference （F=7.62,P=0.01; F=10.34, P=0.005）. The SUV_max and SUV_mean values of ¹²⁵I implant group were significantly lower than the empty seed implant group and the control group while there was no significant difference between the later two groups. And the SUV_max and SUV_mean in ¹²⁵I seed implant group were significantly lower than before treatment, while for the empty seed group and control group there were no significant difference compared with before treatment.Before treatment, tumor necrosis rate of three groups were respectively （9.75±3.10）%, （11.41±5.33）% and （12.46±4.69）%, with no significant difference. 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 （P<0.001）. And the SUV_max values have certain positive correlation with TK1 positive staining index （r=0.85,P=0.001）.Conclusions: Our findings suggest that 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. The efficacy evalution of image-guided ¹²⁵I seed interstitial brachytherapy for advanced pancreatic carcinoma in clinical studyObjective: The purpose of this study was to examine the clinical efficacy of image-guided radioactive iodine-125 (¹²⁵I) seed implantation treatment in patients with unresectable pancreatic cancer.Methods: 40 patients with inoperable pancreatic cancer were enrolled in this study. Of the 40 patients involved in this study, 25 were male, 15 were female, and age ranged from 38 to 89 with 69 on average. Treatment Planning System （TPS） was used to reconstruct 3-Dimensional image of pancreatic tumor and to define the quantity and distribution of ¹²⁵I seeds. ¹²⁵I seeds whose activities ranged 0.5～0.9 mCi/seed were implanted into pancreatic tumor under CT guidance, 1cm apart, avoiding puncturing vessels, pancreatic tube and other nearby organs during the procedure. The tumor matched peripheral dose （MPD） was 31.1～130Gy. Median implanted number of seeds was 36 （range 18-68）, CT scan was done immediately after the procedure to check the quality of the seeds.Results: Median diameter of the tumor was 4.9 cm. Follow-up period was 2 to 30 months. Symptoms of refractory pain were significantly resolved post-interventionally （P<0.05）, and Karnofsky score went up dramatically （P<0.05）. Most often patients reported pain relief 2 to 5 days after implantation. Tumor response which was demonstrated on repeated CT film 2 months post treatment revealed completed relief （CR） in 3 cases, partial relief （PR） in 20 cases, no change （NC） in 14 cases and progression （PD） in 3 cases. Overall responding rate （CR+PR） for this group of patients turned out to be 57.5%. Median survival time for all patients was 10.2 months, while for stage II, stage III, and stage IV were 14.7 months, 10.9 months and 7.1 months respectively. The 6- and 12-month cumulative survival rates were 100%, 88%, 62% and 70%, 41%, 0% by stage subgroup. Elevated serum CA19-9 level before ¹²⁵I seeds implantation were detected in 21 cases, which reduced after 1-3 months.Tumor marker levels significantly reduced compared with that before after ¹²⁵I seed implantation 1 month, and there is significant difference （P <0.05）. 4 seeds of radioactive I-125 were found to migrate to liver in 3 patients. There were no serious complications such as upper GI bleeding, pancreatitis, pancreatic fistula formation and radiation colitis detected during follow-up period.Conclusions: This study suggested that CT-guided brachytherapy using ¹²⁵I seeds implantation is safe, effective, less complicated and can produce adequate pain relief for treating unresectable pancreatic cancer. However, this result required further validation to determine its long-term efficacy.更多还原