Glycolysis on F-18 FDG PET/CT Is Superior to Amino Acid Metabolism on C-11 Methionine PET/CT in Identifying Advanced Renal Cell Carcinoma at Staging

SIMPLE SUMMARY: Alteration of metabolism, including glycolysis and glutaminolysis in malignant tumours, has become a hallmark of cancer and related biological aggressiveness. The metabolic signature of each cancer has been actively investigated for potential new drug development. Of the metabolic imaging biomarkers, F-18 fluorodeoxyglucose (FDG) and C-11 methionine positron emission tomography/computed tomography (PET/CT) are widely studied to evaluate the degree of glucose metabolism and amino acid metabolism, respectively. In this prospective study, we found that both F-18 FDG and C-11 methionine uptakes on PET/CT were heterogeneous in renal cell carcinomas, and increased uptake was associated with higher grades of both radiotracers. Additionally, metabolic tumour volume on F-18 FDG PET/CT but not C-11 methionine PET/CT was significant in predicting advanced-stage renal cell carcinoma. These metabolic features derived with PET/CT may help in the development of new drugs targeting glucose and amino acid metabolic pathways. ABSTRACT: We evaluated the value of F-18 fluorodeoxyglucose (FDG) and C-11 methionine positron emission tomography/computed tomography (PET/CT) to predict high-Fuhrman grade and advanced-stage tumours in patients with renal cell carcinoma (RCC). Forty patients with RCC underwent F-18 FDG and C-11 methionine PET/CT between September 2016 and September 2018. They were classified into limited (stages I and II, n = 15) or advanced stages (stages III and IV, n = 25) according to pathological staging. Logistic regressions were used to predict the advanced stage using various parameters, including maximum standardised uptake value (SUV(max)) and metabolic tumour volume (MTV). Receiver operating characteristic analyses were performed to predict high-grade tumours (Fuhrman 3 and 4). On univariate analysis, tumour size, SUV(max) and MTV of F-18 FDG and C-11 methionine, and Fuhrman grades were significant predictors for the advanced stage. On multivariate analysis, F-18 FDG MTV > 21.3 cm(3) was the most significant predictor (p < 0.001). The area under the curve for predicting high-grade tumours was 0.830 for F-18 FDG (p < 0.001) and 0.726 for C-11 methionine PET/CT (p = 0.014). In conclusion, glycolysis on F-18 FDG PET/CT and amino acid metabolism on C-11 methionine PET/CT were variable but increased in high-grade RCCs. Increased MTV on F-18 FDG PET/CT is a powerful predictor of advanced-stage tumours.