MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Antiangiogenic Treatment.
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Date
2019-06ICR Author
Author
Zormpas-Petridis, K
Jerome, NP
Blackledge, MD
Carceller, F
Poon, E
Clarke, M
McErlean, CM
Barone, G
Koers, A
Vaidya, SJ
Marshall, LV
Pearson, ADJ
Moreno, L
Anderson, J
Sebire, N
McHugh, K
Koh, D-M
Yuan, Y
Chesler, L
Robinson, SP
Jamin, Y
Type
Journal Article
Metadata
Show full item recordAbstract
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 R 2* (second-1) and fractional blood volume (fBV, %) were sensitive imaging biomarkers of hemorrhage and vascular density, respectively, 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.
Subject
Animals
Mice, Transgenic
Humans
Neuroblastoma
Neoplasms, Experimental
Quinazolines
Angiogenesis Inhibitors
Protein Kinase Inhibitors
Contrast Media
Magnetic Resonance Imaging
Treatment Outcome
Prospective Studies
Child
Child, Preschool
Infant
Female
Male
N-Myc Proto-Oncogene Protein
Research team
Computational Pathology & Integrated Genomics
Paediatric Solid Tumour Biology and Therapeutics
Computational Imaging
Pre-Clinical MRI
Language
eng
Date accepted
2019-03-12
License start date
2019-06
Citation
Cancer research, 2019, 79 (11), pp. 2978 - 2991
Publisher
AMER ASSOC CANCER RESEARCH