Johnson S Peter, Ramasawmy Rajiv, Campbell-Washburn Adrienne E, Wells Jack A, Robson Mathew, Rajkumar Vineeth, Lythgoe Mark F, Pedley R Barbara, Walker-Samuel Simon
UCL Cancer Institute, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
UCL Centre for Advanced Biomedical Imaging, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
Br J Cancer. 2016 Apr 12;114(8):897-904. doi: 10.1038/bjc.2016.51. Epub 2016 Mar 31.
Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503.
SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R2(*) MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg(-1) OXi4503.
A significant decrease in SW1222 tumour perfusion was observed (-43±33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R2(*) in LS174T tumours (28±25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits.
Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting.
为了评估对血管靶向(或修饰)疗法的反应,肿瘤血管灌注的非侵入性测量方法是可取的。在本研究中,对肝动脉自旋标记(ASL)磁共振成像(MRI)进行了研究,以测量肝脏中结直肠癌灌注的急性变化,作为对用OXi4503进行血管破坏治疗的反应。
通过脾内注射在MF1 nu/nu小鼠肝脏中建立SW1222和LS174T肿瘤。在给予40mg kg(-1) OXi4503之前和之后90分钟,使用安捷伦9.4T水平孔径扫描仪进行灌注和R2(*) MRI测量。
观察到SW1222肿瘤灌注显著降低(-43±33%,P<0.005)。LS174T肿瘤的基线灌注水平显著较低。固有敏感性MRI显示LS174T肿瘤中的R2(*)显著增加(28±25%,P<0.05)。发现肿瘤灌注变化与大血管的接近程度之间存在关联,治疗前的血流可预测后续反应。组织学评估证实了坏死的发生以及肿瘤沉积物之间异质性反应的证据。
肝脏ASL-MRI可以完全非侵入性地检测对靶向肿瘤血管破坏的急性反应。肝脏肿瘤的肝脏ASL有在临床环境中应用的潜力。