MRI Characterisation of a Novel Transgenic Mouse Model of Neuroblastoma

Introduction Neuroblastoma is the most common extracranial childhood solid tumour, accounting for between 7-10% of paediatric cancers, and originates in peripheral nerve tissues (1). The proto-oncogene MYCN is amplified in 25% of high-risk neuroblastoma and is associated with an aggressive tumour phenotype, enhanced tumour angiogenesis and poor clinical prognosis (2). The Mycn oncoprotein is highly expressed in tumour but not in normal tissue, making it an attractive candidate for targeted therapeutics. To assess the relevance of MYCN overexpression in neuroblastoma, and to test Mycn-targeted therapeutics, a novel murine transgenic model that faithfully replicates the disease biology of high-risk neuroblastoma by targeting overexpression of MYCN to the neural crest has been constructed (3, 4). In this model, tumour origin is spontaneous and occurs in the correct tissue of origin. As a prelude to the assessment of novel therapeutics for the treatment of neuroblastoma, and given their posterior and abdominal localisation, the TH-MYCN model has been investigated by MRI. Specifically, the anatomical presentation and longitudinal development of the tumour in situ, as well as its established response to the chemotherapeutic agent cyclophosphamide in vivo, have been characterised. In addition, quantitative MRI parameters, and interrogation of the tumour vasculature by DCE-MRI, are also reported.