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

J Nucl Med. 2009 Nov;50(11):1815-9. doi: 10.2967/jnumed.109.065367. Epub 2009 Oct 16.

Abstract

Everolimus downregulates glucose metabolism-associated genes in preclinical models. Inhibition of glucose metabolism measured by (18)F-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 (18)F-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 (18)F-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 (18)F-FDG PET.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Aged
  • Biological Transport / drug effects
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Everolimus
  • Female
  • Fluorodeoxyglucose F18 / metabolism*
  • Glucose / metabolism
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Pilot Projects
  • Positron-Emission Tomography
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Kinases / metabolism*
  • Sirolimus / analogs & derivatives*
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases
  • Time Factors

Substances

  • Protein Kinase Inhibitors
  • Fluorodeoxyglucose F18
  • Everolimus
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Glucose
  • Sirolimus