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- Title
DW-MRI as a biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating temozolomide or gemcitabine in glioblastoma.
- Authors
Galbán, Stefanie; Lemasson, Benjamin; Williams, Terence M; Li, Fei; Heist, Kevin A; Johnson, Timothy D; Leopold, Judith S; Chenevert, Thomas L; Lawrence, Theodore S; Rehemtulla, Alnawaz; Mikkelsen, Tom; Holland, Eric C; Galbán, Craig J; Ross, Brian D
- Abstract
The effectiveness of the radiosensitizer gemcitabine (GEM) was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI) for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf(-/-) Pten(loxP/loxP)/Ntv-a RCAS/PDGF(+)/Cre(+)] was treated with gemcitabine (GEM), temozolomide (TMZ) +/- ionizing radiation (IR). Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR) resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials.
- Publication
PloS one, 2012, Vol 7, Issue 4, pe35857
- ISSN
1932-6203
- Publication type
Journal Article
- DOI
10.1371/journal.pone.0035857