Magnetic resonance imaging of ethyl-nitrosourea-induced rat gliomas: A model for experimental therapeutics of low-grade gliomas

Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their pr eventive or therapeutic efficacy in these tumors, requires the use of anima l nobreak models. Spontaneous gliomas develop in models of chemically induc ed carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU ) rat model. However, without the ability to detect initial tumor formation , multiplicity or to measure growth rates, it is difficult to test compound s for their interventional or preventional capabilities. In this study Fish er-334 rats, treated transplacentally with ENU, underwent magnetic resonanc e imaging (MRI) examination in order to evaluate this approach for detectio n of tumor formation and growth. ENU-induced intracranial cerebral tumors w ere first observable in T2-weighted images beginning at 4 months of age and grew with a mean doubling time of 0.487 +/- 0.112 months. These tumors wer e found histologically to be predominately mixed gliomas. Two therapeutic i nterventions were evaluated using MRI, vitamin A (all-trans retinol palmita te, RP), as a chemopreventative agent and the anti-angiogenic drug SU-5416. RP was found to significantly delay the time to first tumor observation by one month (P = 0.05). No differences in rates of tumor formation or growth rates were observed between control and RP-treated groups. MRI studies of rats treated with SU-5416 resulted in reduction in tumor growth rates compa red to matched controls. These results show that MRI can be used to provide novel information relating to the therapeutic efficacy of agents against t he ENU-induced tumor model.