期刊
CANCER RESEARCH
卷 79, 期 11, 页码 2978-2991出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-18-3412
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资金
- Children with Cancer UK Research Fellowship [2014/176]
- Rosetrees Trust grant [M593]
- Children with Cancer UKProject Grant [2014/174]
- Cancer Research UK Program Grant [C34648/A18339, C34648/A14610]
- Instituto de Salud Carlos III [CM12/00260, JR15/00041]
- GOSHCC research leadership award
- Cancer Research UK
- EPSRC
- MRC
- Department of Health (England) [C1060/A10334, C1060/A16464]
- NHS funding
- NIHR GOSH Biomedical Research Centre
- Oak Foundation
- Clinical Research Facility in Imaging
Childhood neuroblastoma is a hypervascular tumor of neural origin, for which antiangiogenic drugs are currently being evaluated; however, predictive biomarkers of treatment response, crucial for successful delivery of precision therapeutics, are lacking. We describe an MRI-pathologic cross-correlative approach using intrinsic susceptibility (IS) and susceptibility contrast (SC) MRI to noninvasively map the vascular phenotype in neuroblastoma Th-MYCN transgenic mice treated with the vascular endothelial growth factor receptor inhibitor cediranib. We showed that the transverse MRI relaxation rate R2 (second 1) and fractional blood volume (fBV, %) were sensitive imaging biomarkers of hemorrhage and vascular density, respective-ly, and were also predictive biomarkers of response to cediranib. Comparison with MRI and pathology from patients with MYCN-amplified neuroblastoma confirmed the high degree to which the Th-MYCN model vascular phenotype recapitulated that of the clinical phenotype, thereby supporting further evaluation of IS-and SC-MRI in the clinic. This study reinforces the potential role of functional MRI in delivering precision medicine to children with neuroblastoma. Significance: This study shows that functional MRI predicts response to vascular-targeted therapy in a genetically engineered murine model of neuroblastoma.
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