VCAM-1-targeted MRI Improves Detection of the Tumor-brain Interface.

Autor:	Cheng VWT; Department of Oncology, University of Oxford, Oxford, United Kingdom.; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., de Pennington N; Department of Oncology, University of Oxford, Oxford, United Kingdom., Zakaria R; Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.; Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom., Larkin JR; Department of Oncology, University of Oxford, Oxford, United Kingdom., Serres S; Department of Oncology, University of Oxford, Oxford, United Kingdom.; School of Life Sciences, University of Nottingham, Nottingham, United Kingdom., Sarkar M; Department of Oncology, University of Oxford, Oxford, United Kingdom., Kirkman MA; Department of Oncology, University of Oxford, Oxford, United Kingdom.; UCL Institute for Education, University College London, London, United Kingdom., Bristow C; Department of Oncology, University of Oxford, Oxford, United Kingdom., Croal P; Mental Health and Clinical Neurosciences & Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.; Nottingham Biomedical Research Centre, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom., Plaha P; Nuffield Department of Surgery, University of Oxford and Department of Neurosurgery, Oxford University Hospitals NHS Trust, Oxford, United Kingdom., Campo L; Nottingham Biomedical Research Centre, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom., Chappell MA; Mental Health and Clinical Neurosciences & Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.; Nottingham Biomedical Research Centre, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom., Lord S; Department of Oncology, University of Oxford, Oxford, United Kingdom., Jenkinson MD; Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom., Middleton MR; Department of Oncology, University of Oxford, Oxford, United Kingdom.; Experimental Cancer Medicine Centre, Department of Oncology, University of Oxford, Oxford, United Kingdom.; Oxford National Institute for Health Research Comprehensive Biomedical Research Centre, Oxford, United Kingdom., Sibson NR; Department of Oncology, University of Oxford, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Jun 01; Vol. 28 (11), pp. 2385-2396.
DOI:	10.1158/1078-0432.CCR-21-4011
Abstrakt:	Purpose: Despite optimal local therapy, tumor cell invasion into normal brain parenchyma frequently results in recurrence in patients with solid tumors. The aim of this study was to determine whether microvascular inflammation can be targeted to better delineate the tumor-brain interface through vascular cell adhesion molecule-1 (VCAM-1)-targeted MRI. Experimental Design: Intracerebral xenograft rat models of MDA231Br-GFP (breast cancer) brain metastasis and U87MG (glioblastoma) were used to histologically examine the tumor-brain interface and to test the efficacy of VCAM-1-targeted MRI in detecting this region. Human biopsy samples of the brain metastasis and glioblastoma margins were examined for endothelial VCAM-1 expression. Results: The interface between tumor and surrounding normal brain tissue exhibited elevated endothelial VCAM-1 expression and increased microvessel density. Tumor proliferation and stemness markers were also significantly upregulated at the tumor rim in the brain metastasis model. T2*-weighted MRI, following intravenous administration of VCAM-MPIO, highlighted the tumor-brain interface of both tumor models more extensively than gadolinium-DTPA-enhanced T1-weighted MRI. Sites of VCAM-MPIO binding, evident as hypointense signals on MR images, correlated spatially with endothelial VCAM-1 upregulation and bound VCAM-MPIO beads detected histologically. These findings were further validated in an orthotopic medulloblastoma model. Finally, the tumor-brain interface in human brain metastasis and glioblastoma samples was similarly characterized by microvascular inflammation, extending beyond the region detectable using conventional MRI. Conclusions: This work illustrates the potential of VCAM-1-targeted MRI for improved delineation of the tumor-brain interface in both primary and secondary brain tumors. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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