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Combined Hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (HyperPET) Estimates of Glycolysis in Canine Cancer Patients

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Abstract

13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare hyperpolarized [1-13C]pyruvate MRS with simultaneous 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET in a cross-sectional study of canine cancer patients. Methods: Canine cancer patients underwent integrated PET/MRI using a clinical whole-body system. Hyperpolarized [1-13C]pyruvate was obtained using dissolution-DNP. 18F-FDG PET, dynamic 13C MRS, 13C MRS Imaging (MRSI) and anatomical 1 H MRI was acquired from 17 patients. Apparent pyruvate-to-lactate rate constants were estimated from dynamic 13C MRS. 18F-FDG Standard Uptake Values and maximum [1-13C]lactate-to-total-13C ratios were obtained from tumor regions of interest. Following inspection of data, patients were grouped according to main cancer type and linear regression between measures of lactate generation and 18FFDG uptake were tested within groups. Between groups, the same measures were tested for group differences. Results: The main cancer types of the 17 patients were sarcoma (n = 11), carcinoma (n = 5) and mastocytoma (n = 1). Significant correlations between pyruvate-to-lactate rate constants and 18F-FDG uptake were found for sarcoma patients, whereas no significant correlations appeared for carcinoma patients. The sarcoma patients showed a non-significant trend towards lower 18F-FDG uptake and higher lactate generation than carcinoma patients. However, the ratio of lactate generation to 18F-FDG uptake was found to be significantly higher in sarcoma as compared to carcinoma. The results were found both when lactate generation was estimated as an apparent pyruvate-to-lactate rate constant from dynamic 13C MRS and as an [1-13C]lactate to total 13C ratio from 13C MRSI. Conclusions: A comparison of hyperpolarized [1-13C]pyruvate MRS with simultaneous 18F-FDG PET indicate that lactate generation and 18F-FDG uptake in cancers can be related and that their relation depend on cancer type. This finding could be important for the interpretation and eventual clinical implementation of hyperpolarized 13C. In addition, the differences between the two modalities may allow for better metabolic phenotyping performing hybrid imaging in the form of hyperPET