Detection of brain tumours using translational molecularly targeted magnetic resonance imaging
1Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford,, Oxford, UK
Recent advances in molecularly-targeted magnetic resonance imaging (MRI) offer a number of advantages over conventional methodologies, including identification of specific molecular processes, such as upregulation of vascular cell adhesion molecule 1 (VCAM-1), that may be particularly active in the invasive margins of brain tumour. The aim of this study was to determine whether VCAM-1-targeted MRI could facilitate improved spatial delineation of tumour margins and more accurate assessment of tumour activity in brain tumour.
Three cohorts of nude rats were injected intracerebrally with either a metastatic human breast carcinoma cell line, a multiform glioblastoma cell line, or with a desmoplastic medulloblastoma cell line. All animals underwent clinical T1- and T2-weighted to assess tumour growth and blood-brain barrier (BBB) integrity. For VCAM-1-targeted MRI, animals underwent T2* gradient echo 3D MRI after injection of microparticles of iron oxide (MPIO) functionalised with either an anti-VCAM-1 antibody (VCAM-MPIO) or a control IgG antibody (IgG-MPIO). Immunohistochemical assessment was also performed post-mortem.
: In all cases, brain tumours exhibited a compromised BBB using post-gadolinium T1-weighted imaging. Additionally, marked hypointensities were evident on T2*-weighted MRI following intravenous injection of VCAM-MPIO, but not IgG-MPIO, and this was particularly evident at the margins of the tumours. VCAM-1 upregulation detected immunohistochemically was significantly greater on blood vessels associated with the tumour margins than the tumour core, and co-localised with proliferative regions of the tumour. Spatial comparison of VCAM-MPIO binding and gadolinium-enhanced signal, using a 3D composite analysis method, indicated clearer delineation of tumour margins with the molecularly-targeted approach.
These findings suggest that VCAM-1-targeted MRI may enable improved detection of tumour margins, as compared to the current clinical gadolinium-enhanced MRI, for both primary and secondary tumours in the brain and, thus, provide a sensitive biomarker for effective surgical resection and/or radiotherapy in brain tumour patients.