Burrell Jake S, Walker-Samuel Simon, Boult Jessica K R, Baker Lauren C J, Jamin Yann, Halliday Jane, Waterton John C, Robinson Simon P
*Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research, Surrey †Centre for Advanced Biomedical Imaging, Department of Medicine and Institute of Child Health, University College London, London ‡R&D Personalised Healthcare & Biomarkers, AstraZeneca, Alderley Park, Macclesfield, UK.
Top Magn Reson Imaging. 2016 Oct;25(5):237-243. doi: 10.1097/RMR.0000000000000102.
The aim of this study was to use the combined carbogen-ultrasmall superparamagnetic iron oxide (CUSPIO) magnetic resonance imaging (MRI) method, which uses spatial correlations in independent susceptibility imaging biomarkers, to investigate and compare the impact of tumor size and anatomical site on vascular structure and function in vivo. Mice bearing either subcutaneous or orthotopic PC3 LN3 prostate tumors were imaged at 7 T, using a multi-gradient echo sequence to quantify R2, before and during carbogen (95% O2/5% CO2) breathing, and subsequently following intravenous administration of USPIO particles. Carbogen and USPIO-induced changes in R2 were used to inform on hemodynamic vasculature and fractional blood volume (%), respectively. The CUSPIO imaging data were also segmented to identify and assess five categories of R2 response. Small and large subcutaneous and orthotopic tumor cohorts all exhibited significantly (P < 0.05) different median baseline R2, ΔR2carbogen, and fractional blood volume. CUSPIO imaging showed that small subcutaneous tumors predominantly exhibited a negative ΔR2carbogen followed by a positive ΔR2USPIO, consistent with a well perfused tumor vasculature. Large subcutaneous tumors exhibited a small positive ΔR2carbogen and relatively low fractional blood volume, suggesting less functional vasculature. Orthotopic tumors revealed a large, positive ΔR2carbogen, consistent with vascular steal, and which may indicate that vascular function is more dependent on site of implantation than tumor size. Regions exhibiting significant ΔR2carbogen, but no significant ΔR2USPIO, suggesting transient vascular shutdown over the experimental timecourse, were apparent in all 3 cohorts. CUSPIO imaging can inform on efficient drug delivery via functional vasculature in vivo, and on appropriate tumor model selection for pre-clinical therapy trials.
本研究的目的是使用联合的碳合气-超小超顺磁性氧化铁（CUSPIO）磁共振成像（MRI）方法，该方法利用独立的磁化率成像生物标志物中的空间相关性，在体内研究和比较肿瘤大小及解剖部位对血管结构和功能的影响。对皮下或原位植入PC3 LN3前列腺肿瘤的小鼠在7T磁场下进行成像，使用多梯度回波序列在呼吸碳合气（95% O2/5% CO2）之前、期间和随后静脉注射超小超顺磁性氧化铁颗粒后对R2进行定量。碳合气和超小超顺磁性氧化铁引起的R2变化分别用于反映血流动力学血管系统和血容量分数（%）。CUSPIO成像数据也进行了分割，以识别和评估五类R2反应。皮下和原位的小肿瘤组及大肿瘤组均表现出显著不同（P<0.05）的中位基线R2、ΔR2碳合气和血容量分数。CUSPIO成像显示，皮下小肿瘤主要表现为负的ΔR2碳合气，随后是正的ΔR2超小超顺磁性氧化铁，这与灌注良好的肿瘤血管系统一致。皮下大肿瘤表现出小的正ΔR2碳合气和相对较低的血容量分数，提示血管功能较差。原位肿瘤显示出大的正ΔR2碳合气，与血管窃血一致，这可能表明血管功能更依赖于植入部位而非肿瘤大小。在所有3个肿瘤组中均明显存在一些区域，这些区域表现出显著的ΔR2碳合气，但没有显著的ΔR2超小超顺磁性氧化铁，提示在实验过程中出现短暂的血管关闭。CUSPIO成像可用于了解体内通过功能性血管系统进行的有效药物递送情况，以及为临床前治疗试验选择合适的肿瘤模型。
