[Proc Amer Assoc Cancer Res, Volume 47, 2006]
Tumor Biology 18: Animal Models of Human Cancers 3: Central Nervous System and Imaging |
Abstract #2746
Diffusion MRI early prediction of survival using solvent facilitated perfusion of BCNU in a rat model of glioma
Patrick McConville,
Jonathan B. Moody,
Richard J. Lister,
William L. Elliott,
Wilbur R. Leopold, III,
Brian D. Ross,
Alnawaz Rehemtulla,
John M. Young and
Edward E. Luck
MIR Preclinical Services, Inc., Ann Arbor, MI, University of Michigan, Ann Arbor, MI, Direct Therapeutics, Inc., Redwood City, CA
INTRODUCTION: Solvent facilitated perfusion (SFP) after intratumoral (IT) injection is a promising therapy for high grade glioma, but the need exists for non-invasive and clinically translatable means to reliably and rapidly assess different solvent types. Diffusion MRI (DMRI) can characterize early changes in cellularity in a responding tumor, and has been shown to be an early predictor of efficacy and survival. We used DMRI in a comparison of IT injection of BCNU dissolved in 50 µl of (i) ethanol (EtOH) (DTI-015) and (ii) 50%EtOH/50%PEG400, in rat 9L glioma. METHODS: Male Fisher rats were implanted with 9L intracranial glioma, and divided into treatment groups (see Table). DMRI assessment of tumor volume and apparent diffusion coefficient (ADC) was performed before treatment, then 1, 2, 6, 10, 20, 30, 45, 60, 75 and 90 days after treatment. Rats with complete tumor regression following treatment, that persisted to the study end, were designated as cures. RESULTS AND DISCUSSION: The BCNU SFP treatments produced a similar, early increase in ADC, before tumor regression. The tumor growth curves for the treatment groups were indistinguishable. The ADC for the EtOH/PEG group decreased to baseline more rapidly than that for the EtOH group, suggesting more rapid tumor repopulation, which correlated with lower cure rate and decreased lifespan in this group (see Table). CONCLUSION: DMRI determined ADC was predictive of efficacy and survival, even distinguishing the two highly efficacious SFP therapies within 14 days of treatment. DMRI is an efficient means for rapid screening of new SFP treatments, and may be translated for early prediction of efficacy in clinical trials that test SFP therapies.
Copyright © 2006 by the American Association for Cancer Research.
