Detection of Early Response to Temozolomide Treatment in Brain Tumors Using Hyperpolarized C-13 MR Metabolic Imaging

Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Journal of Magnetic Resonance Imaging (Impact Factor: 3.21). 06/2011; 33(6):1284-90. DOI: 10.1002/jmri.22563
Source: PubMed

ABSTRACT To demonstrate the feasibility of using DNP hyperpolarized [1-(13)C]-pyruvate to measure early response to temozolomide (TMZ) therapy using an orthotopic human glioblastoma xenograft model.
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). (13)C 3D magnetic resonance spectroscopic imaging (MRSI) data were acquired following injection of 2.5 mL (100 mM) hyperpolarized [1-(13)C]-pyruvate using a 3T scanner prior to treatment (day D0), at D1 (days from treatment) or D2.
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).
The results from this study suggest that metabolic imaging with hyperpolarized [1-(13)C]-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.

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    • "[1- 13 C]Pyruvate also has relatively longer í µí±‡1 relaxation time and rapid transport into the cells for subsequent metabolism [96]. Hyperpolarized [1- 13 C]pyruvate has been used to study the real-time flux of pyruvate to lactate noninvasively following anticancer therapies in xenograft models [97] [98] [99] [100] [101]. The first clinical trial of DNP-MRS has recently demonstrated the use of hyperpolarized [1- 13 C]pyruvate to examine prostate cancer metabolism in human [47] (Figure 1), and it paves the way to rapid translation of this exciting technology to clinical research and perhaps clinical practice [96]. "
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    03/2014; 2014:625095. DOI:10.1155/2014/625095
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    • "The duration of data acquisition was 60 s (12 temporally resolved images for each metabolite). This imaging approach allows the imaging window to be extended beyond a shorter (10–20 s), fixed window centered around a presumed temporal maximum of metabolites used in prior 13C MR spectroscopic imaging studies [6]–[8]. The magnitude images of 13C pyruvate and lactate were reconstructed by the default MR scanner software (k-space data were zero filled to 128×128 in plane matrix prior to Fourier transform). "
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