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Lack of Correlation of Hypoxic Cell Fraction and Angiogenesis with Glucose Metabolic Rate in Non–Small Cell Lung Cancer Assessed by ¹⁸F-Fluoromisonidazole and ¹⁸F-FDG PET

¹ Centre for PET, Austin Hospital, Heidelberg, Victoria, Australia; ² Ludwig Institute for Cancer Research, Austin Hospital, Heidelberg, Victoria, Australia; ³ Department of Thoracic Surgery, Austin Hospital, Heidelberg, Victoria, Australia; ⁴ Division of Bioinformatics, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and ⁵ Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia

Correspondence: For correspondence or reprints contact: Andrew M. Scott, MD, Centre for PET, and Ludwig Institute for Cancer Research, 1st Floor, Harold Stokes Bldg., Austin Hospital, Studley Rd., Heidelberg, Victoria 3084, Australia. E-mail: andrew.scott{at}ludwig.edu.au

PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed non–small cell lung cancer (NSCLC) for the presence of hypoxia, as indicated by the uptake of ¹⁸F-fluoromisonidazole (¹⁸F-FMISO), and to examine the relationship of hypoxia to the uptake of ¹⁸F-FDG, microvessel density, and other molecular markers of hypoxia. Methods: Twenty-one patients with suspected or biopsy-proven NSCLC were enrolled prospectively in this study. All patients had PET studies with ¹⁸F-FMISO and ¹⁸F-FDG. Seventeen patients subsequently underwent surgery, with analysis performed for tumor markers of angiogenesis and hypoxia. Results: In the 17 patients with resectable NSCLC (13 men, 4 women; age range, 51–77 y), the mean ¹⁸F-FMISO uptake in tumor was significantly lower than that of ¹⁸F-FDG uptake (P < 0.0001) and showed no correlation with ¹⁸F-FDG uptake (r = 0.26). The mean (95% confidence interval [CI]) ¹⁸F-FMISO SUV_max (maximum standardized uptake value) was 1.20 [0.95–1.45] compared with the mean [95% CI] ¹⁸F-FDG SUV_max of 5.99 [4.62–7.35]. The correlation between ¹⁸F-FMISO uptake, ¹⁸F-FDG uptake, and tumor markers of hypoxia and angiogenesis was poor. A weakly positive correlation between ¹⁸F-FMISO and ¹⁸F-FDG uptake and Ki67 was found. Conclusion: The hypoxic cell fraction of primary NSCLC is consistently low, and there is no significant correlation in NSCLC between hypoxia and glucose metabolism in NSCLC assessed by ¹⁸F-FDG. These findings have direct implications in understanding the role of angiogenesis and hypoxia in NSCLC biology.

Key Words: PET • tumor hypoxia • non–small cell lung cancer • immunohistochemistry • vascular endothelial growth factor

COPYRIGHT © 2006 by the Society of Nuclear Medicine, Inc.

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