Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer.
Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer.
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DOI：
10.1038/s41598-017-08838-6
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发表时间：
2017-08-14
影响因子：
4.6
通讯作者：
Caravan P
中科院分区：
文献类型：
--
作者：
Polasek M;Yang Y;Schühle DT;Yaseen MA;Kim YR;Sung YS;Guimaraes AR;Caravan P
I型胶原过多的纤维化是许多实体肿瘤的标志，纤维化是癌症治疗的一个有希望的靶点，但缺乏用于非侵入性量化的工具。在这里，我们使用了以Gd为基础的针对I型胶原(EP-3533)的探针的磁共振成像来成像和量化胰腺导管腺癌的纤维化。与健康胰腺相比，原位同基因小鼠模型导致肿瘤的胶原蛋白水平高出2.3倍。动物在静脉注射前、中和最多60 分钟以4.7 T进行扫描。注射EP-3533或其非结合异构体EP-3612。体外定量显示，与EP-3612相比，肿瘤对EP-3533的摄取明显更高，但在周围组织(血液、肌肉)中则没有。在T1加权MRI上显示的EP-3533摄取与二次谐波成像确定的胶原的空间分布有很好的相关性。EP-3533和EP-3612在肿瘤药代动力学方面的差异被用来区分与肿瘤胶原蛋白的特异性结合和非特异性摄取。基于曲线下面积的无模型药代动力学测量被确认为纤维化的可靠成像生物标记物。使用EP-3533的胶原靶向分子MRI为肿瘤组织中纤维化的非侵入性可视化和量化提供了一种新的工具。
Fibrosis with excessive amounts of type I collagen is a hallmark of many solid tumours, and fibrosis is a promising target in cancer therapy, but tools for its non-invasive quantification are missing. Here we used magnetic resonance imaging with a gadolinium-based probe targeted to type I collagen (EP-3533) to image and quantify fibrosis in pancreatic ductal adenocarcinoma. An orthotopic syngeneic mouse model resulted in tumours with 2.3-fold higher collagen level compared to healthy pancreas. Animals were scanned at 4.7 T before, during and up to 60 min after i.v. injection of EP-3533, or of its non-binding isomer EP-3612. Ex-vivo quantification of gadolinium showed significantly higher uptake of EP-3533 compared to EP-3612 in tumours, but not in surrounding tissue (blood, muscle). Uptake of EP-3533 visualized in T1-weighted MRI correlated well with spatial distribution of collagen determined by second harmonic generation imaging. Differences in the tumour pharmacokinetic profiles of EP-3533 and EP-3612 were utilized to distinguish specific binding to tumour collagen from non-specific uptake. A model-free pharmacokinetic measurement based on area under the curve was identified as a robust imaging biomarker of fibrosis. Collagen-targeted molecular MRI with EP-3533 represents a new tool for non-invasive visualization and quantification of fibrosis in tumour tissue.
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影响因子：
11.5
作者：
Armstrong, T;Packham, G;Iredale, JP
通讯作者：
Iredale, JP
影响因子：
11.2
作者：
Grossman, Moran;Ben-Chetrit, Nir;Sagi, Irit
通讯作者：
Sagi, Irit
DOI：
10.1158/1078-0432.ccr-15-2010
发表时间：
2016-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hingorani SR;Harris WP;Beck JT;Berdov BA;Wagner SA;Pshevlotsky EM;Tjulandin SA;Gladkov OA;Holcombe RF;Korn R;Raghunand N;Dychter S;Jiang P;Shepard HM;Devoe CE
通讯作者：
Devoe CE
DOI：
10.1126/science.1176009
发表时间：
2009-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hynes RO
通讯作者：
Hynes RO
影响因子：
4.3
作者：
Cox TR;Erler JT
通讯作者：
Erler JT