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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

¹ Lung Cancer Group Cologne, Department I of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne, Germany; ² Department of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands; ³ Department of Nuclear Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne, Germany; ⁴ Novartis Pharma AG, Basel, Switzerland; ⁵ Novartis Pharmaceuticals Corp., East Hanover, New Jersey; ⁶ Department of Radiology, Center for Integrated Oncology, University Hospital Cologne, Cologne, Germany; ⁷ Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; ⁸ Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max-Planck Society and the Medical Faculty of the University Cologne, Cologne, Germany; ⁹ Chemical Genomics Center of the Max Planck Society, Dortmund, Germany; and ¹⁰ Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

Correspondence: For correspondence or reprints contact: Jürgen Wolf, Lung Cancer Group Cologne, Department I of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, 50924 Cologne, Germany. E-mail: juergen.wolf{at}uk-koeln.de

Everolimus downregulates glucose metabolism–associated genes in preclinical models. Inhibition of glucose metabolism measured by ¹⁸F-FDG PET was postulated to serve as a pharmacodynamic 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 variety of summed standardized uptake value (SUV) measures. Both maximum and mean SUVs were used, with normalizations to body surface area and body weight and with and without correcting 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 –12.8% to –72.2%. Conclusion: These observations demonstrate that inhibition of glucose metabolism is an early effect of everolimus treatment in NSCLC patients and can be assessed using ¹⁸F-FDG PET.

Key Words: everolimus • positron emission tomography • ¹⁸F-FDG • lung cancer

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