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Published on: June 7, 2020
VCAM-1-targeted MRI Improves Detection of the Tumor-brain Interface
Vinton W T Cheng1,2, Nicholas de Pennington1, Rasheed Zakaria3,4
1Department of Oncology, University of Oxford, Oxford, United Kingdom.
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.
Insights
Targeted MRI using vascular cell adhesion molecule-1 (VCAM-1) effectively highlights the tumor-brain interface in brain tumors. This approach reveals microvascular inflammation beyond conventional imaging, improving tumor delineation and potentially reducing recurrence.
Area of Science:
- Neuro-oncology
- Medical Imaging
- Molecular Biology
Background:
- Tumor cell invasion into brain parenchyma leads to frequent recurrence despite optimal therapy.
- Accurate delineation of the tumor-brain interface is crucial for effective treatment.
Purpose of the Study:
- To investigate if targeting microvascular inflammation via vascular cell adhesion molecule-1 (VCAM-1)-targeted MRI can improve tumor-brain interface delineation.
- To assess the efficacy of VCAM-1-targeted MRI in detecting the tumor-brain interface in preclinical models and human samples.
Main Methods:
- Utilized xenograft rat models of breast cancer brain metastasis and glioblastoma.
- Examined human brain metastasis and glioblastoma margins for endothelial VCAM-1 expression.
- Employed VCAM-1-targeted MRI (VCAM-MPIO) and compared it with conventional MRI (Gd-DTPA T1-weighted).
Main Results:
- Elevated endothelial VCAM-1 expression and increased microvessel density were observed at the tumor-brain interface.
- VCAM-1-targeted MRI highlighted the tumor-brain interface more effectively than conventional MRI.
- Histological analysis confirmed VCAM-MPIO binding correlated with VCAM-1 upregulation at the interface.
Conclusions:
- VCAM-1-targeted MRI shows promise for enhanced delineation of the tumor-brain interface in primary and secondary brain tumors.
- This technique can identify microvascular inflammation beyond the visible tumor margins.
- Improved delineation may lead to better treatment strategies and reduced tumor recurrence.
