Downregulation of 18F-FDG Uptake in PET as an Early Pharmacodynamic Effect in Treatment of Non–Small Cell Lung Cancer with the mTOR Inhibitor Everolimus

Everolimus downregulates glucose metabolism–associated genes in preclinical models. Inhibition of glucose metabolism measured by 18F-FDGPETwas postulated to serve as a pharma-codynamic marker in everolimus-treated non–small cell lung cancer (NSCLC) patients.Methods: In 8 NSCLC patients treated with everolimus, the percentage change in 18F-FDG PET uptake (days 8 and 28 relative to baseline) was determined using a vari-ety of summed standardized uptake value (SUV) measures. Both maximum and mean SUVs were used, with normalizations to body surface area and bodyweight andwith andwithout correct-ing for plasma glucose levels. Results: In 5 patients, a reduction of 18F-FDG PET uptake on day 8 was observed with all methods, ranging from 212.8 % to 272.2%. Conclusion: These observa-tions demonstrate that inhibition of glucose metabolism is an early effect of everolimus treatment in NSCLC patients and ca