Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer
Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer
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DOI：
10.1097/00006676-200007000-00054
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发表时间：
2000-07-01
期刊：
影响因子：
2.9
通讯作者：
Sarkar, FH
中科院分区：
文献类型：
--
作者：
He, ZQ;Evelhoch, JL;Sarkar, FH
胰腺癌是美国最无法治愈、最致命的人类癌症之一。为了促进新的治疗药物的开发，我们先前建立了一个接近于人类胰腺癌自然生物学行为的原位胰腺肿瘤模型。在这项研究中，磁共振成像(MRI)技术被开发出来，以非侵入性地检测肿瘤的形成并连续监测肿瘤生长动力学，用于实验药物测试。通过使用优化的T2加权成像方法，我们能够区分人胰腺癌和正常小鼠胰腺。肿瘤细胞移植后第11天即可检测到原位肿瘤的形成，肿瘤体积小至12 mm(3)。有肿瘤证据的小鼠被分成四个处理组：对照组、Auristatin-PE组、吉西他滨及其联合治疗组。治疗结束后，这些小鼠在实验结束前至少接受了三次成像。将MRI肿瘤体积测量结果与活检时的肿瘤重量进行比较，相关系数为0.98。从一系列磁共振成像(MRI)测量构建的肿瘤生长曲线清楚地表明，与对照组相比，治疗组小鼠的肿瘤生长受到抑制。正如预期的那样，联合用药组的有效率比单独使用奥司他丁-PE或吉西他滨的有效率最高，且数据具有高度统计学意义(p<；0.004)。根据这些结果，我们得出结论，无创性MRI可用于监测该原位人胰腺肿瘤模型的系列治疗反应，并可用于未来在人体研究之前评估新型抗肿瘤药物。
Pancreatic cancer is one of the most incurable and lethal human cancers in the United States. To facilitate development of novel therapeutic agents, we previously established an orthotopic pancreatic tumor model that closely mimics the natural biological behavior of human pancreatic cancer. In this study, magnetic resonance imaging (MRI) techniques were developed to detect tumor formation noninvasively and monitor serially tumor growth kinetics in this orthotopic model used for experimental drug testing. By using an optimized T2-weighted imaging method, we were able to distinguish human pancreas cancer from normal mouse pancreas. Orthotopic tumor formation was detected as early as day 11 after tumor cell implantation with a tumor volume as small as 12 mm(3). Mice with evidence of tumor were separated into four treatment groups: control, auristatin-PE, gemcitabine, and their combination. After treatment, the mice were imaged at least three times before termination of the experiment. Comparison between MRI tumor volume measurements and tumor weights made at biopsy resulted in a correlation coefficient of 0.98. The tumor growth curves constructed from serial magnetic resonance imaging (MRI) measurements clearly showed tumor growth inhibition in treated mice compared with the control group. As expected, the group treated with the combination had the highest response rate compared with either auristatin-PE or gemcitabine alone, and the data were statistically highly significant (p < 0.004). From these results, we conclude that noninvasive MRI can be used to monitor serially therapeutic response in this orthotopic human pancreatic tumor model and can be used in the future to evaluate novel antitumor agents before human studies.