Molecular Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
University of Campania Luigi Vanvitelli, Caserta, Italy.
Magn Reson Med. 2021 Aug;86(2):995-1007. doi: 10.1002/mrm.28778. Epub 2021 Mar 25.
The aim of this study was to investigate two clinically approved plasma volume expanders (dextran 70 and voluven) as macromolecular MRI-chemical exchange saturation transfer (CEST) contrast agents to assess tumor vascular properties.
CEST contrast efficiency of both molecules (6% w/v) was measured in vitro at various irradiation saturation powers (1-6 μT for 5 s) and pH values (range, 5.5-7.9) and the exchange rate of hydroxyl protons was calculated. In vivo studies in a murine adenocarcinoma model (n = 4 mice for each contrast agent) upon i.v. injection provided CEST-derived perfusion tumor properties that were compared with those obtained with a gadolinium-based blood-pool agent (Gd-AAZTA-Madec).
In vitro measurements showed a marked CEST contrast dependency to pH, with higher CEST contrast at lower pH values for both molecules. The measured prototropic exchange rates confirmed a base-catalyzed exchange rate that was faster for dextran 70 in comparison to voluven. Both molecules showed a similar CEST contrast increase (ΔST% > 3%) in the tumor tissue up to 30 min postinjection, with heterogeneous accumulation. In tumors receiving both CEST and T -weighted agents, a voxel-by-voxel analysis indicated moderate spatial correlation of perfusion properties between voluven/dextran 70 and Gd-AAZTA-Madec, suggesting different distribution patterns according to their molecular size.
The obtained results showed that both voluven and dextran 70 can be exploited as MRI-CEST contrast agents for evaluating tumor enhancement properties. Their increased accumulation in tumors and prolonged contrast enhancement promote their use as blood-pool MRI-CEST agents to examine tumor vascularization.
本研究旨在探讨两种临床批准的血浆扩容剂（右旋糖酐 70 和贺斯）作为大分子 MRI-化学交换饱和传递（CEST）对比剂，以评估肿瘤血管特性。
在不同的辐照饱和功率（1-6μT 持续 5s）和 pH 值（范围 5.5-7.9）下，测量了两种分子（6%w/v）的 CEST 对比效率，并计算了羟基质子的交换率。在静脉注射后，在小鼠腺癌模型中进行的体内研究（每种对比剂 4 只小鼠）提供了 CEST 衍生的灌注肿瘤特性，将其与基于钆的血池造影剂（Gd-AAZTA-Madec）获得的特性进行了比较。
体外测量显示 pH 值对 CEST 对比度有显著依赖性，两种分子在较低 pH 值下的 CEST 对比度更高。测量的质子交换率证实了一种由碱基催化的交换率，与贺斯相比，右旋糖酐 70 的交换率更快。两种分子在注射后 30 分钟内都在肿瘤组织中表现出类似的 CEST 对比度增加（ΔST%>3%），呈不均匀聚集。在同时接受 CEST 和 T1 加权造影剂的肿瘤中，体素对体素分析表明，贺斯/右旋糖酐 70 和 Gd-AAZTA-Madec 的灌注特性之间存在中等空间相关性，这表明根据其分子大小，存在不同的分布模式。
研究结果表明，贺斯和右旋糖酐 70 均可作为 MRI-CEST 对比剂，用于评估肿瘤增强特性。它们在肿瘤中的积累增加和延长的对比增强促进了它们作为血池 MRI-CEST 造影剂的使用，以检查肿瘤血管生成。
