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INTRODUCTION: RCAS/tv-a technology relies on somatic gene transfer through infection by RCAS viral vectors derived from the avian retrovirus A (ALV-A) in mice expressing the gene for the RCAS receptor (tv-a). The nestin tv-a (Ntv-a) mouse, which expresses tv-a under the control of the nestin promoter in glial-progenitors, when infected with ALV virus encoding PDGF, spontaneously develops glioma by 3 weeks of age in almost 100% of cases [1]. Using this model, we correlated T2-weighted (T2w) anatomical and contrast-enhanced (CE) MRI with histology and survival in untreated mice. METHODS: 40 Ntv-a mice with PDGF-induced brain tumors at 3 weeks of age, underwent weekly T2w and CE MRI, using multi-slice fast spin-echo and spin-echo sequences, respectively. In both cases, contiguous, 0.5 mm thick, transaxial slices were used to cover the entire tumor. After 4 weeks, half of the mice were sacrificed for histology, with the remaining mice kept on study for survival. RESULTS AND DISCUSSION: Tumors were well delineated in T2w images, showing features (including pseudopalisades, necrosis and cyst) that were typical of human glioblastoma multiforme (GBM) in 32% of cases (mean doubling time of 11 ± 1 days), and oligodendroglioma (mean doubling time of 19 ± 2 days) in the remaining cases. The MRI data was well correlated with histology. In GBMs only, CE MRI showed ring enhancement, and T2w images showed necrotic regions, both typical of the human condition. By a combination of initial T2w and CE MRI at 3-4 weeks age, MRI was predictive of tumor grade, and ultimately correlated with survival. CONCLUSION: The Ntv-a mouse constitutes a promising model of human glioma, in which MRI is able to delineate heterogeneities due to localized regions of highly cellular tumor, necrosis, edema, cyst and abnormal vasculature, as in the human disease. MRI correlated with histology and was predictive of survival in this model. MRI methodology in the Ntv-a mouse may provide an efficient preclinical means for testing novel therapies, and optimizing new combination strategies for treatment of glioma. REFERENCE: [1] Shih, et al. (2004) Cancer Res, 64, 14:4783-9

[Proc Amer Assoc Cancer Res, Volume 46, 2005]