Detection of brain tumours using translational molecularly targeted magnetic resonance imaging

S├ębastien Serres1,Matthew Kirkman1,Nick de Pennington1,Claire Bristow1,Nicola R Sibson1

1Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford,, Oxford, UK

Presenting date: Monday 2 November
Presenting time: 16.10-16.25

Background

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.

Method

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.

Results

: 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.

Conclusion

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.