Biological correlates of FDG uptake in non-small cell lung cancer

de Geus-Oei, Lioe-Fee; Krieken, J. Han J.M. van; Aliredjo, Riena P.; Krabbe, Paul F.M.; Frielink, Cathelijne; Verhagen, Ad F.T.; Boerman, Otto C.; Oyen, Wim J.G.

doi:10.1016/j.lungcan.2006.08.018

« Previous Next »Lung Cancer
Volume 55, Issue 1 , Pages 79-87, January 2007

Biological correlates of FDG uptake in non-small cell lung cancer

Lioe-Fee de Geus-Oei
- Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
- Corresponding author at: Department of Nuclear Medicine (internal postal code 444), Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 24 3614048; fax: +31 24 3618942.
J. Han J.M. van Krieken
- Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Riena P. Aliredjo
- Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Paul F.M. Krabbe
- Department of Medical Technology Assessment, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Cathelijne Frielink
- Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Ad F.T. Verhagen
- Department of Cardio-Thoracic Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Otto C. Boerman
- Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Wim J.G. Oyen
- Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Received 24 March 2006; received in revised form 25 August 2006; accepted 29 August 2006.

Summary

Purpose

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).

Conclusion

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.

Keywords: Early stage NSCLC, FDG-PET, SUV, GLUT, Hexokinase, Caspase-3, Tumor size