MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Anti-angiogenic Treatment

• Published in: Cancer research (Chicago, Ill.) Ill.), 2019-03, Vol.79 (11), p.2978-2991
• Main Authors: Zormpas-Petridis, Konstantinos, Jerome, Neil P., Blackledge, Matthew D., Carceller, Fernando, Poon, Evon, Clarke, Matthew, McErlean, Ciara M., Barone, Giuseppe, Koers, Alexander, Vaidya, Sucheta J., Marshall, Lynley V., Pearson, Andrew D.J., Moreno, Lucas, Anderson, John, Sebire, Neil, McHugh, Kieran, Koh, Dow-Mu, Yuan, Yinyin, Chesler, Louis, Robinson, Simon P., Jamin, Yann
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-18-3412

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-pathological cross-correlative approach using intrinsic susceptibility (IS-) and susceptibility contrast (SC-) MRI to non-invasively 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 * (s -1 ) and fractional blood volume f BV (%) 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.