Haeck Joost, Bol Karin, Bison Sander, van Tiel Sandra, Koelewijn Stuart, de Jong Marion, Veenland Jifke, Bernsen Monique
Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Department of Medical Informatics, Erasmus Medical Centre, Rotterdam, The Netherlands.
Contrast Media Mol Imaging. 2015 Nov-Dec;10(6):413-20. doi: 10.1002/cmmi.1643. Epub 2015 May 21.
Anti-tumor efficacy of targeted peptide-receptor radionuclide therapy (PRRT) relies on several factors, including functional tumor vasculature. Little is known about the effect of PRRT on tumor vasculature. With dynamic contrast-enhanced (DCE-) MRI, functional vasculature is imaged and quantified using contrast agents. In small animals DCE-MRI is a challenging application. We optimized a clinical sequence for fast hemodynamic acquisitions, time-resolved imaging of contrast kinetics (TRICKS), to obtain DCE-MRI images at both high spatial and high temporal resolution in mice and rats. Using TRICKS, functional vasculature was measured prior to PRRT and longitudinally to investigate the effect of treatment on tumor vascular characteristics. Nude mice bearing H69 tumor xenografts and rats bearing syngeneic CA20948 tumors were used to study perfusion following PRRT administration with (177) lutetium octreotate. Both semi-quantitative and quantitative parameters were calculated. Treatment efficacy was measured by tumor-size reduction. Optimized TRICKS enabled MRI at 0.032 mm(3) voxel size with a temporal resolution of less than 5 s and large volume coverage, a substantial improvement over routine pre-clinical DCE-MRI studies. Tumor response to therapy was reflected in changes in tumor perfusion/permeability parameters. The H69 tumor model showed pronounced changes in DCE-derived parameters following PRRT. The rat CA20948 tumor model showed more heterogeneity in both treatment outcome and perfusion parameters. TRICKS enabled the acquisition of DCE-MRI at both high temporal resolution (Tres ) and spatial resolutions relevant for small animal tumor models. With the high Tres enabled by TRICKS, accurate pharmacokinetic data modeling was feasible. DCE-MRI parameters revealed changes over time and showed a clear relationship between tumor size and Ktrans .
靶向肽受体放射性核素治疗（PRRT）的抗肿瘤疗效取决于多个因素，包括功能性肿瘤血管系统。目前对PRRT对肿瘤血管系统的影响知之甚少。通过动态对比增强（DCE-）MRI，可使用造影剂对功能性血管系统进行成像和定量分析。在小动物中，DCE-MRI是一项具有挑战性的应用。我们优化了一种用于快速血流动力学采集的临床序列，即对比剂动力学时间分辨成像（TRICKS），以在小鼠和大鼠中获得高空间分辨率和高时间分辨率的DCE-MRI图像。使用TRICKS，在PRRT之前测量功能性血管系统，并进行纵向研究以探讨治疗对肿瘤血管特征的影响。使用携带H69肿瘤异种移植物的裸鼠和携带同基因CA20948肿瘤的大鼠，研究用（177）镥奥曲肽进行PRRT给药后的灌注情况。计算了半定量和定量参数。通过肿瘤大小缩小来衡量治疗效果。优化后的TRICKS能够以0.032 mm³的体素大小、小于5秒的时间分辨率和大体积覆盖范围进行MRI检查，这比常规临床前DCE-MRI研究有了显著改进。肿瘤对治疗的反应反映在肿瘤灌注/渗透参数的变化上。H69肿瘤模型在PRRT后DCE衍生参数有明显变化。大鼠CA20948肿瘤模型在治疗结果和灌注参数方面表现出更多的异质性。TRICKS能够在与小动物肿瘤模型相关的高时间分辨率（Tres）和空间分辨率下采集DCE-MRI。借助TRICKS实现的高Tres，准确的药代动力学数据建模是可行的。DCE-MRI参数随时间显示出变化，并显示出肿瘤大小与Ktrans之间的明确关系。
