Combined hyperpolarized ¹³C-pyruvate MRS and ¹⁸F-FDG PET (hyperPET) estimates of glycolysis in canine cancer patients

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 ¹H 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 ¹⁸F-FDG 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.