Bioluminescence imaging (BLI) offers a rapid and accurate means for longitudinal study of intracranial tumor growth and response to therapy in rodent models. In this study we show for the first time the application of BLI to evaluating the efficacy of salvage therapy for recurrent supratentorial xenografts in athymic mice. To accomplish this, a highly invasive, patient-derived glioblastoma multiforme (GBM) xenograft, GBM 14, was modified for bioluminescence imaging via transduction with luciferase-encoding lentivirus. Mice receiving intracranial injection of luciferase-modified GBM 14 were randomized into control and TMZ treatment groups, with TMZ treatment consisting of a single dose of 120 mg/kg. Extent of intracranial tumor was followed by weekly BLI, which showed a consistent pattern of increasing signal in control mice, and regression followed by regrowth in the treatment group. At a time when BLI indicated tumor recurrence in treated animals (40 days after initial treatment), half of the treated mice received an additional 120 mg/kg dose of TMZ. BLI readings for mice receiving the initial dose only (TMZ 1x group) were contrasted with the salvage therapy group (TMZ 2x). BLI results were consistent with the corresponding survival results, and the imaging data provided a much earlier determination of tumor response to therapy. Although the extent of additional survival benefit from salvage therapy was much less than that associated with initial treatment (i.e., 56.2 days increased mean survival for 1x vs. control, but only 21.8 additional days for 2x vs. 1x), it was nonetheless statistically significant (p=0.009). These results are consistent with the conclusions of a recently published clinical study whose results indicate benefit for a small group of patients with recurrent high-grade glioma that were retreated with TMZ. More generally, the results of this experiment support the utility of BLI for testing secondary or salvage therapies against recurrent GBM.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA