DCE-MRI using small-molecular and albumin-binding contrast agents in experimental carcinomas with different stromal content
DCE-MRI using small-molecular and albumin-binding contrast agents in experimental carcinomas with different stromal content
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DOI：
10.1016/j.ejrad.2009.04.043
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发表时间：
2011-04-01
影响因子：
3.3
通讯作者：
Marzola, Pasquina
中科院分区：
文献类型：
--
作者：
Farace, Paolo;Merigo, Flavia;Marzola, Pasquina
目的：比较使用标准小分子（Gd-DTPA）和白蛋白结合（MS-325）造影剂在两种不同基质含量癌模型中的DCE-MRI实验。材料与方法：裸鼠皮下注射DU-145或BXPC-3癌细胞。接种后约2周，通过大量注射Gd-DTPA或MS-325进行DCE-MRI。为了定量分析，在每个肿瘤上手动绘制感兴趣的体积。为了解决非均匀增强问题，每个肿瘤体积被分成20%最增强部分和其余80%最不增强部分。在这些选定的肿瘤体积上计算平均肿瘤增强，并在肿瘤组和造影剂之间进行比较。差分增强图、峰值增强图和峰值时间图用于视觉评价。行CD31和VEGF免疫组化。结果：在80%最小增强体积内，动态扫描后期，MS-325诱导BXPC-3肿瘤的平均增强高于DU-145肿瘤。在20%的最大增强体积中，使用任何一种造影剂，两种肿瘤类型之间的显著差异仅在早期观察到，而在动态扫描的后期时间点，BXPC-3肿瘤中观察到的更快的冲洗掩盖了差异。增强图证实BXPC-3肿瘤的特征是使用任何一种造影剂都有明显的冲洗率，特别是在高增强的外周边缘。MS-325的这种洗脱模式似乎是BXPC-3癌特有的，因为在DU-145肿瘤中没有观察到。最后，在两种肿瘤类型中，MS-325在动态扫描的后期产生明显高于Gd-DTPA的增强。离体分析证实BXPC-3肿瘤中明显存在异常浸润间质，肿瘤血管嵌入其中。在所有的肿瘤中，中心部分比周围区域存活更少，间质组织浸润更少。结论：对比剂分布与基质含量有关，可能是基质含量导致BXPC-3肿瘤增强程度较高、洗脱速度较快的原因。特别是，“早期”增强MRI是检测间质含量高的肿瘤部位（即BXPC-3肿瘤的外周边缘）最敏感的技术。由于最近使用FDG- pet成像研究了相同的肿瘤模型，显示FDG摄取与间质含量呈反比关系，因此对比增强MRI和FDG- pet可以在评估肿瘤方面提供互补和全面的敏感性。2009爱思唯尔爱尔兰有限公司版权所有。
Objectives: To compare DCE-MRI experiments performed using a standard small-molecular (Gd-DTPA) and an albumin-binding (MS-325) contrast agent in two carcinoma models with different stromal content.Materials and methods: DU-145 or BXPC-3 cancer cells were subcutaneously injected into nude mice. DCE-MRI was performed by a bolus injection of Gd-DTPA or MS-325 about 2 weeks after inoculation. For quantitative analysis a volume of interest was manually drawn over each tumor. To address the heterogeneous enhancement, each tumor volume was then divided into the 20% most-enhancing and the remaining 80% least-enhancing fractions. Mean tumor enhancement was calculated over these selected tumor volumes and compared between tumor groups and contrast agents. Maps of differential enhancement, peak enhancement and time-to-peak were used for visual evaluation. CD31 and VEGF immunohistochemistry were performed in excised tumors.Results: In the 80% least-enhancing volume, at late time points of the dynamic scan, the mean enhancement elicited by MS-325 was higher in BXPC-3 than in DU-145 tumors. In the 20% most-enhancing volume, using either contrast agents, significant difference between the two tumors types were observed only early, while at later time points of the dynamic scan the difference were obscured by the faster washout observed in the BXPC-3 tumors. Enhancement maps confirmed that BXPC-3 tumors were characterized by marked washout rate using either contrast agent, particularly in the higher enhancing peripheral rim. With MS-325 this washout pattern appeared to be specific to the BXPC-3 carcinomas, since it was not observed in the DU-145 tumors. Finally, in both tumor types, MS-325 produced significantly higher enhancement than Gd-DTPA in the late phase of the dynamic scan. Ex vivo analysis confirmed the marked presence of aberrant infiltrative stroma in BXPC-3 tumors, in which tumor vessels were embedded. In all tumors the central portion was less viable and less infiltrated by stromal tissue then the peripheral areas.Conclusions: Contrast distribution proved to be related to stromal content, which presumably produced the higher enhancement and faster washout observed in the BXPC-3 tumors. In particular, 'early' contrast-enhanced MRI, appeared as the most sensitive technique to detect the tumor portions characterized by a high stromal content, i.e. the peripheral rim of the BXPC-3 tumors. Since the same tumor models were recently investigated using FDG-PET imaging, showing inverse relationship between FDG uptake and stromal content, contrast-enhanced MRI and FDG-PET could provide complementary and comprehensive sensitivity in the assessment of carcinomas. (C) 2009 Elsevier Ireland Ltd. All rights reserved.