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

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.