The impact of calorie-limited diets on the detectability of renal cell carcinomas by positron emission tomography with 2-deoxy-2-18F-fluoro-D-glucose

1209 Introduction: The Impact of Calorie-Restricted Diets on the Detectability of Renal Cell Carcinomas by Positron Emission Tomography with 2-Deoxy-2-[18F]Fluoro-D-Glucose Objectives: Renal cell carcinoma (RCC) is the most common kidney tumor type in adults. Although scans of magnetic resonance imaging (MRI) and computed tomography (CT) have been in clinical practice of kidney cancer, the role of positron emission tomography (PET) has not been established likely due to the physiological nature of the kidneys, from which [18F]FDG (2-deoxy-2-[18F]fluoro-D-glucose) is excreted. Given the fact that glycolysis is highly active in RCC tumors and serves as the major energy source1,2, we reason that limiting calorie intake might be able to enhance the imaging contrast of RCCs with [18F]FDG as it suppresses the glycolysis rates in normal tissues3,4. Herein we present a pilot study to test our hypothesis that the [18F]FDG-PET detectability of RCC tumors could be enhanced by calorie restriction conditions. Methods: Patient-derived xenograft (PDX) models of RCC were developed in NOD-SCID mice by two lines. One (XP164) is a clear cell renal cell carcinoma (ccRCC), which represents >80% of all RCC cases, the other (XP152) is a rare hereditary leiomyomatosis and renal cell cancer (HLRCC) that is fumarase deficient. One week after the tumor implantation, a group of tumor-bearing mice (n = 5) were fed with a calorie-restricted diet (CRD, 6.7 Kcal/day) for two weeks while another group of tumor-bearing mice (n = 5) were fed with normal chow (NC). Mice were fasted for 16 hours before injected 100 μCi of [18F]FDG for PET scans. The uptake of [18F]FDG in tumor region and normal kidney was quantified. Results: Two weeks of CRD significantly increased blood ketone body levels in both PDX models (XP164: NC: 0.55 ± 0.13 mM; CRD: 1.95 ± 0.48 mM, n = 4, P = 0.0076; XP152: NC: 1.18 ± 0.83 mM; CRD: 3.46 ± 0.62 mM, n = 5, P = 0.0014). The diet alteration did not affect fasted blood glucose levels. We observed that CRD significantly enhanced the uptake of [18F]FDG in the XP152 xenografts (NC: 11.80 ± 2.61 %ID/g; CRD: 17.62 ± 3.55 %ID/g, n = 5, P = 0.020), leading to an increased PET signal ratio of tumor/kidney in the CRD group (NC: 2.17 ± 1.05; CRD: 5.20 ± 2.11 , n = 5, P = 0.029). However, CRD did not increase the uptake of [18F]FDG in the XP164 tumors, but a trend of increased tumor/kidney was observed in the XP164 subcutaneous tumor model (NC, 1.19 ± 0.16; CRD, 1.59 ± 0.35, n = 4, P = 0.098). The 2.5-fold increase of tumor/kidney ratio in XP152 PDX model likely resulted from the high energy dependency of XP152 on glycolysis. The smaller increase of tumor/kidney ratio in XP164 PDX model can be attributed to the better metabolic flexibility of XP164. Conclusions: Our study demonstrates that CRD significantly increased the tumor/normal tissue PET signal ratio in fumarase-deficient XP152 PDX in NOD-SCID mice, which suggests the potential of using CRD to enhance the detectability of [18F]FDG-PET of RCC tumors in clinical diagnosis and treatment assessment. Acknowledgements: This work was partially supported by grants from the Cancer Prevention and Research Institute of Texas (RP170638) and NIH (P50 CA196516).