Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona, Italy.
Eur J Radiol. 2011 Apr;78(1):52-9. doi: 10.1016/j.ejrad.2009.04.043. Epub 2009 May 13.
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.
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.
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.
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.
比较两种不同基质含量的癌模型中使用标准小分子（Gd-DTPA）和白蛋白结合（MS-325）造影剂进行的 DCE-MRI 实验。
DU-145 或 BXPC-3 癌细胞皮下注射到裸鼠中。在接种后约 2 周，通过 Gd-DTPA 或 MS-325 的推注进行 DCE-MRI。为了进行定量分析，手动在每个肿瘤上绘制感兴趣的体积。为了解决异质增强的问题，然后将每个肿瘤体积分为增强程度最高的 20%和增强程度最低的 80%部分。在这些选定的肿瘤体积上计算平均肿瘤增强，并比较肿瘤组和对比剂之间的差异。差异增强图、峰值增强图和达峰时间图用于视觉评估。在切除的肿瘤中进行 CD31 和 VEGF 免疫组织化学染色。
在动态扫描的晚期，在 80%最低增强体积中，MS-325 引起的平均增强在 BXPC-3 肿瘤中高于 DU-145 肿瘤。在 20%最高增强体积中，使用两种造影剂，仅在早期观察到两种肿瘤类型之间的显著差异，而在动态扫描的后期，由于 BXPC-3 肿瘤的洗脱速度更快，差异被掩盖。增强图证实，使用两种造影剂，BXPC-3 肿瘤的洗脱率均较高，尤其是在较高增强的外周边缘。使用 MS-325，这种洗脱模式似乎是 BXPC-3 癌的特异性，因为在 DU-145 肿瘤中未观察到。最后，在两种肿瘤类型中，MS-325 在动态扫描的晚期产生的增强均高于 Gd-DTPA。离体分析证实，BXPC-3 肿瘤中存在明显的异常浸润性基质，其中包含肿瘤血管。在所有肿瘤中，中央部分的活力和间质组织浸润程度均低于周围区域。
对比剂分布与基质含量有关，这可能导致 BXPC-3 肿瘤中观察到的更高增强和更快洗脱。特别是，“早期”对比增强 MRI 似乎是检测高基质含量肿瘤部分（即 BXPC-3 肿瘤的外周边缘）最敏感的技术。由于最近使用 FDG-PET 成像对相同的肿瘤模型进行了研究，显示 FDG 摄取与基质含量之间呈反比关系，因此增强 MRI 和 FDG-PET 可以在评估癌方面提供互补和全面的敏感性。
