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Effects of fasting on serial measurements of hyperpolarized [1-(13) C]pyruvate metabolism in tumors.

ABSTRACT: Imaging of the metabolism of hyperpolarized [1-(13) C]pyruvate has shown considerable promise in preclinical studies in oncology, particularly for the assessment of early treatment response. The repeatability of measurements of (13) C label exchange between pyruvate and lactate was determined in a murine lymphoma model in fasted and non-fasted animals. The fasted state showed lower intra-individual variability, although the [1-(13) C]lactate/[1-(13) C]pyruvate signal ratio was significantly greater in fasted than in non-fasted mice, which may be explained by the higher tumor lactate concentrations in fasted animals. These results indicate that the fasted state may be preferable for the measurement of (13) C label exchange between pyruvate and lactate, as it reduces the variability and therefore should make it easier to detect the effects of therapy. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

SUBMITTER: Serrao EM

PROVIDER: S-EPMC4973679 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Effects of fasting on serial measurements of hyperpolarized [1-(13) C]pyruvate metabolism in tumors.

Serrao Eva M EM Rodrigues Tiago B TB Gallagher Ferdia A FA Kettunen Mikko I MI Kennedy Brett W C BW Vowler Sarah L SL Burling Keith A KA Brindle Kevin M KM

NMR in biomedicine 20160616 8

Imaging of the metabolism of hyperpolarized [1-(13) C]pyruvate has shown considerable promise in preclinical studies in oncology, particularly for the assessment of early treatment response. The repeatability of measurements of (13) C label exchange between pyruvate and lactate was determined in a murine lymphoma model in fasted and non-fasted animals. The fasted state showed lower intra-individual variability, although the [1-(13) C]lactate/[1-(13) C]pyruvate signal ratio was significantly grea ...[more]

PMID: 27309986

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Project description:BackgroundThree-dimensional (3D) multiecho balanced steady-state free precession (ME-bSSFP) has previously been demonstrated in preclinical hyperpolarized (HP) 13 C-MRI in vivo experiments, and it may be suitable for clinical metabolic imaging of prostate cancer (PCa).PurposeTo validate a signal simulation framework for the use of sequence parameter optimization. To demonstrate the feasibility of ME-bSSFP for HP 13 C-MRI in patients. To evaluate the metabolism in PCa measured by ME-bSSFP.Study typeRetrospective single-center cohort study.Phantoms/populationPhantoms containing aqueous solutions of [1-13 C] lactate (2.3 M) and [13 C] urea (8 M). Eight patients (mean age 67 ± 6 years) with biopsy-confirmed Gleason 3 + 4 (n = 7) and 4 + 3 (n = 1) PCa. FIELD STRENGTH/SEQUENCES: 1 H MRI at 3 T with T2 -weighted turbo spin-echo sequence used for spatial localization and spoiled dual gradient-echo sequence used for B0 -field measurement. ME-bSSFP sequence for 13 C MR spectroscopic imaging with retrospective multipoint IDEAL metabolite separation.AssessmentThe primary endpoint was the analysis of pyruvate-to-lactate conversion in PCa and healthy prostate regions of interest (ROIs) using model-free area under the curve (AUC) ratios and a one-directional kinetic model (kP ). The secondary objectives were to investigate the correlation between simulated and experimental ME-bSSFP metabolite signals for HP 13 C-MRI parameter optimization.Statistical testsPearson correlation coefficients with 95% confidence intervals and paired t-tests. The level of statistical significance was set at P < 0.05.ResultsStrong correlations between simulated and empirical ME-bSSFP signals were found (r > 0.96). Therefore, the simulation framework was used for sequence optimization. Whole prostate metabolic HP 13 C-MRI, observing the conversion of pyruvate into lactate, with a temporal resolution of 6 seconds was demonstrated using ME-bSSFP. Both assessed metrics resulted in significant differences between PCa (mean ± SD) (AUC = 0.33 ± 012, kP = 0.038 ± 0.014) and healthy (AUC = 0.15 ± 0.10, kP = 0.011 ± 0.007) ROIs.Data conclusionMetabolic HP 13 C-MRI in the prostate using ME-bSSFP allows for differentiation between aggressive PCa and healthy tissue.Evidence level2 TECHNICAL EFFICACY: Stage 1.

Dataset Information

Effects of fasting on serial measurements of hyperpolarized [1-(13) C]pyruvate metabolism in tumors.

Publications

Effects of fasting on serial measurements of hyperpolarized [1-(13) C]pyruvate metabolism in tumors.

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