Detection of early response to temozolomide treatment in brain tumors using hyperpolarized 13C MR metabolic imaging

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Abstract
Purpose: To demonstrate the feasibility of using DNP hyperpolarized [1‐13C]‐pyruvate to measure early response to temozolomide (TMZ) therapy using an orthotopic human glioblastoma xenograft model.Materials and Methods: Twenty athymic rats with intracranial implantation of human glioblastoma cells were divided into two groups: one group received an oral administration of 100 mg/kg TMZ (n = 10) and the control group received vehicle only (n = 10). 13C 3D magnetic resonance spectroscopic imaging (MRSI) data were acquired following injection of 2.5 mL (100 mM) hyperpolarized [1‐13C]‐pyruvate using a 3T scanner prior to treatment (day D0), at D1 (days from treatment) or D2.Results: Tumor metabolism as assessed by the ratio of lactate to pyruvate (Lac/Pyr) was significantly altered at D1 for the TMZ‐treated group but tumor volume did not show a reduction until D5 to D7. The percent change in Lac/Pyr from baseline was statistically different between the two groups at D1 and D2 (P < 0.008), while percent tumor volume was not (P > 0.2).Conclusion: The results from this study suggest that metabolic imaging with hyperpolarized [1‐13C]‐pyruvate may provide a unique tool that clinical neuro‐oncologists can use in the future to monitor tumor response to therapy for patients with brain tumors. J. Magn. Reson. Imaging 2011;33:1284–1290.

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