Department of Radiology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China.
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Magn Reson Med. 2019 Oct;82(4):1471-1479. doi: 10.1002/mrm.27818. Epub 2019 May 20.
Vascular disrupting therapy of cancer has become a promising approach not only to regress tumor growth directly but also to boost the delivery of chemotherapeutics in the tumor. An imaging approach to monitor the changes in tumor vascular permeability, therefore, has important applications for monitoring of vascular disrupting therapies.
Mice bearing CT26 subcutaneous colon tumors were injected intravenously with 150 kD dextran (Dex150, diameter, d~ 20 nm, 375 mg/kg), tumor necrosis factor-alpha (TNF-α; 1 µg per mouse), or both (n = 3 in each group). The Z-spectra were acquired before and 2 h after the injection, and the chemical exchange saturation transfer (CEST) signals in the tumors as quantified by asymmetric magnetization transfer ratio (MTR ) at 1 ppm were compared.
The results showed a significantly stronger CEST contrast enhancement at 1 ppm (∆MTR = 0.042 ± 0.002) in the TNF-α-treated tumors than those by Dex150 alone (∆MTR = 0.000 ± 0.005, P = 0.0229) or TNF-α alone (∆MTR = 0.002 ± 0.004, P = 0.0264), indicating that the TNF-α treatment strongly augmented the tumor uptake of 150 kD dextran. The MRI findings were verified by fluorescence imaging and immunofluorescence microscopy.
High molecular weight dextrans can be used as safe and sensitive CEST MRI contrast agents for monitoring tumor response to vascular disrupting therapy and, potentially, for developing dextran-based theranostic drug delivery systems.
血管破坏疗法不仅可以直接使肿瘤生长消退，而且可以增强肿瘤内化疗药物的递送，因此已成为一种很有前途的方法。因此，一种监测肿瘤血管通透性变化的成像方法对于监测血管破坏疗法具有重要的应用价值。
将 CT26 皮下结肠肿瘤的小鼠静脉内注射 150 kD 葡聚糖（Dex150，直径 d~20nm，375mg/kg）、肿瘤坏死因子-α（TNF-α；每只小鼠 1μg）或两者（每组 3 只）。在注射前和注射后 2 h 采集 Z 光谱，并比较肿瘤中的化学交换饱和传递（CEST）信号，通过不对称磁化传递比（MTR）在 1 ppm 下定量。
结果表明，与单独使用 Dex150（∆MTR = 0.000 ± 0.005，P = 0.0229）或单独使用 TNF-α（∆MTR = 0.002 ± 0.004，P = 0.0264）相比，TNF-α 处理的肿瘤中在 1 ppm 处的 CEST 对比增强明显更强（∆MTR = 0.042 ± 0.002），表明 TNF-α 治疗强烈增强了肿瘤对 150 kD 葡聚糖的摄取。MRI 结果通过荧光成像和免疫荧光显微镜得到验证。
高分子量葡聚糖可用作安全且灵敏的 CEST MRI 对比剂，用于监测肿瘤对血管破坏治疗的反应，并可能用于开发基于葡聚糖的治疗药物递送系统。
