Intrabiliary RF Heat-enhanced Local Chemotherapy of a Cholangiocarcinoma Cell Line: Monitoring with Dual-Modality Imaging-Preclinical Study
Intrabiliary RF Heat-enhanced Local Chemotherapy of a Cholangiocarcinoma Cell Line: Monitoring with Dual-Modality Imaging-Preclinical Study
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DOI：
10.1148/radiol.13130866
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发表时间：
2014-02-01
期刊：
影响因子：
19.7
通讯作者：
Yang, Xiaoming
中科院分区：
文献类型：
--
作者：
Zhang, Feng;Le, Thomas;Yang, Xiaoming
目的：探讨磁共振(MR)热导丝介导射频(RF)热疗能否增强吉西他滨和5-氟尿嘧啶(5-FU)对胆管癌细胞系的治疗效果以及化疗药物在猪胆总管(CBD)壁上的局部沉积剂量。材料和方法：动物实验方案经动物护理与使用委员会批准。用绿色荧光蛋白标记的人胆管癌细胞和24只小鼠胆管癌细胞用(A)联合化疗(吉西他滨和5-Fu)加射频热疗，(B)单纯化疗，(C)单纯射频热疗，或(D)磷酸盐缓冲液生理盐水治疗。用14.0-T磁共振成像和光学成像对细胞增殖进行量化，并监测肿瘤随时间的变化。为了进一步验证技术可行性，使用微孔球囊进行了吉西他滨和5-FU的胆道内局部给药，其中8头猪进行了射频热疗，8头猪进行了射频热疗。用高压液相色谱定量测定胆管壁的化疗沉积剂量。采用非参数Mann-Whitney U检验和配对样本Wilcoxon符号秩次检验。结果：联合治疗较单纯化疗和单纯射频热疗诱导的细胞平均增殖水平更低(0.39+/-0.13[标准差]vs0.87+/-0.10和1.03+/-0.13，P<；.001)。联合治疗相对肿瘤体积小于单纯化疗和单纯射频热疗(0.65+/-0.03vs1.30+/-0.021和1.37+/-0.05，P=.001)。仅在联合治疗组中，MR成像和光学成像在治疗后立即显示肿瘤肿块中的表观扩散系数和荧光信号显著减少。经胆道射频热疗后，胆管壁的平均药物沉积剂量明显高于未经胆道射频热疗的(吉西他滨：0.32 mg/g组织+/-0.033 vs 0.260 mg/g+/-0.030；5-FU：0.660 mg/g+/-0.060 vs 0.52 mg/g+/-0.050，P<；0.05)。结论：胆道内射频热疗可提高人胆管癌细胞系的化疗效果，促进药物在猪胆总管组织的局部沉积。
Purpose: To determine whether magnetic resonance (MR) imaging heating guidewire-mediated radiofrequency (RF) hyperthermia could enhance the therapeutic effect of gemcitabine and 5-fluorouracil (5-FU) in a cholangiocarcinoma cell line and local deposit doses of chemotherapeutic drugs in swine common bile duct (CBD) walls.Materials and Methods: The animal protocol was approved by the institutional animal care and use committee. Green fluorescent protein-labeled human cholangiocarcinoma cells and cholangiocarcinomas in 24 mice were treated with (a) combination therapy with chemotherapy (gemcitabine and 5-FU) plus RF hyperthermia, (b) chemotherapy only, (c) RF hyperthermia only, or (d) phosphate-buffered saline. Cell proliferation was quantified, and tumor changes over time were monitored with 14.0-T MR imaging and optical imaging. To enable further validation of technical feasibility, intra-biliary local delivery of gemcitabine and 5-FU was performed by using a microporous balloon with (eight pigs) or without (eight pigs) RF hyperthermia. Chemotherapy deposit doses in the bile duct walls were quantified by means of high-pressure liquid chromatography. The non-parametric Mann-Whitney U test and the paired-sample Wilcoxon signed rank test were used for data analysis.Results: Combination therapy induced lower mean levels of cell proliferation than chemotherapy only and RF hyperthermia only (0.39 +/- 0.13 [standard deviation] vs 0.87 +/- 0.10 and 1.03 +/- 0.13, P < .001). Combination therapy resulted in smaller relative tumor volume than chemotherapy only and RF hyperthermia only (0.65 +/- 0.03 vs 1.30 +/- 0.021 and 1.37 +/- 0.05, P =.001). Only in the combination therapy group did both MR imaging and optical imaging show substantial decreases in apparent diffusion coefficients and fluorescent signals in tumor masses immediately after the treatments. Chemotherapy quantification showed a higher average drug deposit dose in swine CBD walls with intra-biliary RF hyperthermia than without it (gemcitabine: 0.32 mg/g of tissue +/- 0.033 vs 0.260 mg/g +/- 0.030 and 5-FU: 0.660 mg/g +/- 0.060 vs 0.52 mg/g +/- 0.050, P < .05).Conclusion: The use of intrabiliary MR imaging heating guidewire-mediated RF hyperthermia can enhance the chemotherapeutic effect on a human cholangiocarcinoma cell line and local drug deposition in swine CBD tissues.