Biological correlates of FDG uptake in non-small cell lung cancer.
OBJECTIVE
Each pathological stage of non-small cell lung cancer (NSCLC) consists of a heterogeneous population containing patients at much higher risk than others. Noninvasive functional imaging modalities, such as 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), could play a role in further characterization of NSCLCs. As many factors can influence the extent of FDG uptake, the underlying mechanisms for FDG accumulation in tumors, are still a matter of debate. The aim of the present study was to investigate these possible mechanisms in the primary site of early stage preoperatively untreated NSCLC.


METHODS
19 patients with early stage NSCLC, who had undergone both preoperative FDG-PET imaging and curative surgery, were enrolled in this study. Standardized uptake values (SUVs) were used for evaluation of primary tumor FDG uptake. Final diagnosis, tumor type, tumor cell differentiation and size of the primary tumors were confirmed histopathologically in resected specimens. Histologic sections were analyzed for amount of inflammation and necrosis. Expression of the glucose membrane transporters (GLUT-1 and GLUT-3); the isoforms of the glycolytic enzyme hexokinase (HK-I, HK-II and HK-III); and the cysteine protease caspase-3, was evaluated immunohistochemically.


RESULTS
FDG uptake was significantly higher in squamous cell carcinomas (mean SUV 13.4+/-4.9, n=8) compared to adenocarcinomas (7.1+/-3.3, n=8, p=0.007), or large cell carcinomas (5.9+/-1.9, n=3, p=0.02). The degree of FDG accumulation seemed to depend especially on GLUT-1, GLUT-3 and tumor cell differentiation. The summed standardized values of these three parameters correlated significantly with the SUV (r=0.47, p=0.05).


CONCLUSIONS
The present study supports the hypothesis that tumor cell differentiation in combination with overexpression of GLUT-1 and GLUT-3 determine the extent of FDG accumulation and that squamous cell carcinomas accumulate more FDG than adenocarcinomas or large cell carcinomas.
de Geus-Oei
Lioe-Fee
LF
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. L.degeus-oei@nucmed.umcn.nl
van Krieken
J Han J M
JH
Aliredjo
Riena P
RP
Krabbe
Paul F M
PF
Frielink
Cathelijne
C
Verhagen
Ad F T
AF
Boerman
Otto C
OC
Oyen
Wim J G
WJ
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D051272:Glucose Transporter Type 1 / Q000235:genetics; D051273:Glucose Transporter Type 2 / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18