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 (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%.


CONCLUSIONS
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.
Nogová
Lucia
L
Lung Cancer Group Cologne, Department I of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne, Germany.
Boellaard
Ronald
R
Kobe
Carsten
C
Hoetjes
Nikie
N
Zander
Thomas
T
Gross
Stefan Hubert
SH
Dimitrijevic
Sasa
S
Pellas
Theodore
T
Eschner
Wolfgang
W
Schmidt
Katja
K
Bangard
Christopher
C
Hayes
Wendy
W
Thomas
Roman K
RK
Dietlein
Markus
M
Giaccone
Giuseppe
G
Hoekstra
Otto S
OS
Lammertsma
Adriaan A
AA
Wolf
Jürgen
J
D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D000068338:Everolimus; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
D047428:Protein Kinase Inhibitors; D019788:Fluorodeoxyglucose F18; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D005947:Glucose; D020123:Sirolimus