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

Abstract

A B S T R A C TF-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 18 F-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 18 F-FDG uptake and higher lactate generation than carcinoma patients. However, the ratio of lactate generation to 18 F-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 13 C MRS and as an [1-13 C]lactate to total 13 C ratio from 13 C MRSI. This finding could be important for the interpretation and eventual clinical implementation of hyperpolarized 13 C. In addition, the differences between the two modalities may allow for better metabolic phenotyping performing hybrid imaging in the form of hyperPET. Conclusions

Pyruvate‐lactate exchange and glucose uptake in human prostate cancer cell models. A study in xenografts and suspensions by hyperpolarized [1‐13C]pyruvate MRS and [18F]FDG‐PET

“…In another study, on canine tumors, in which [ 18 F]FDG-PET and pyruvate-to-lactate exchange were combined across animals, neither SUV nor k pl values could differentiate between carcinomas and sarcomas, although the ratio of k pl over SUV mean was significantly higher in sarcomas than in the carcinomas, which was taken as indicating a difference in contribution of the Warburg effect to energy metabolism in these tumors. 59 The k pl /SUV ratio in our study was significantly higher in the LNCaP compared with the PC3 tumors.…”

“…A study in dogs showed a positive correlation between the label exchange rate between pyruvate and lactate and [ 18 F]FDG uptake in sarcoma lesions, but not in carcinomas. 58,59 In a subcutaneous hepatocellular carcinoma model, no correlation of pyruvate and lactate parameters with physiologic or histologic parameters was found. 62 Studies comparing [ 18 F] FDG-PET and [1-13 C]pyruvate MR measurements before and after treatment showed an earlier decline in pyruvate to lactate exchange rate compared with decline in [ 18 F]FDG uptake.…”

“…This suggests that glucose and/or pyruvate metabolism is different from that observed in other tumor types for which combined [ 18 F]FDG-PET and hyperpolarized [1- 13 C] pyruvate MRS revealed a positive correlation between measures of pyruvate to lactate conversion and glucose uptake, or no correlation at all. 41,[59][60][61] For example, in a subcutaneous rat breast cancer model, tumors with similar apparent diffusion coefficients (ADCs) showed a significant positive correlation between the label exchange rate k pl between pyruvate and lactate and [ 18 F]FDG standard uptake values. 41 A (significant) weak negative correlation was found between ADC values and SUV mean and a trend towards a weak negative correlation between ADC values and k pl .…”

Advanced Cancer Imaging Applied in the Comparative Setting

“…Access to such patients supports multiparametric imaging studies in a tractable period of time within their clinical management. Other examples of novel tracer development and application by inclusion of companion species include 13-C pyruvate magnetic resonance spectroscopy (21), and 18 F-tetrafluoroborate ( 18 F-BF − 4 or 18 F-TFB) for expressed sodium-iodide symporter (NIS) PET imaging (Figure 4), which could be a useful tool for clinical thyroid and neuroendocrine tumor imaging, for preclinical imaging of NIS-expressing disease models and for cell trafficking studies (22)(23)(24). We have also explored the utility of an 18 F-radiolabeled fatty acid 18 F-fluoro-thia-heptadecandoic acid for metabolic imaging of fatty acid oxidation, which is an emerging field in the study of cancer metabolism (Figure 5) (25,26).…”

Simultaneous characterization of tumor cellularity and the Warburg effect with PET, MRI and hyperpolarized 13C-MRSI

“…So far, only a few sites worldwide attempted to assess the flux of glucose through the glycolytic pathway either sequentially or simultaneously with FDG-PET and pyruvate imaging (HyperPET 25 - 28 ). Witney et al .…”