Abstract
Background: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.Methods: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.Results: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.Conclusions: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.
Highlights
Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting therapies
Angiogenesis is a key hallmark of cancer biology (Hanahan and Weinberg, 2011), and while this enables the delivery of nutrients and oxygen to meet the metabolic demands of the malignant cells, it provides a route through which to administer therapeutic agents
The development of non-invasive measures of vascular perfusion in tumours is appropriate as the conventional radiological assessment of response evaluates changes in tumour size, which overlooks functional changes that can occur over much shorter timescales and could be indicative of a successful response to the therapy
Summary
The aim of this research was to evaluate whether ASL can provide a direct measure of tumour perfusion for prognostic measurements both before and at an acute time point after vascular targeted therapy. The aim of this study was to evaluate the response of a model of liver metastasis to vascular disruption using hepatic ASL-MRI to measure tumour perfusion, alongside IS-MRI as a measure of deoxyhaemoglobin accumulation
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