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Correlation of Hypoxic Cell Fraction and Angiogenesis with Glucose Metabolic Rate in Gliomas Using ¹⁸F-Fluoromisonidazole, ¹⁸F-FDG PET, and Immunohistochemical Studies

¹ Centre for PET, Austin Hospital, Heidelberg, Victoria, Australia; ² Ludwig Institute for Cancer Research, Austin Hospital, Heidelberg, Victoria, Australia; ³ Departments of Surgery, Urology, and Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia; and ⁴ Division of Genetics and Bioinformatics, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

Correspondence: For correspondence or reprints contact: Andrew M. Scott, MD, Centre for PET, Level 1, Harold Stokes Bldg., Austin Hospital, 145-163 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 primary brain tumors 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 and molecular markers of hypoxia. Methods: Seventeen patients with suspected primary glioma were enrolled prospectively in this study. Sixteen patients had histology, with 2 having metastatic disease. All patients had PET studies with ¹⁸F-FMISO and ¹⁸F-FDG and MRI studies. Immunohistochemistry was undertaken with tumor markers of angiogenesis and hypoxia. Patients were monitored for disease progression and statistical analysis of data was performed. Results: Of the 14 patients with histology, 8 died with a median time of 16 mo (range, 2–30 mo) until death. Of those who died, 7 had positive and 1 had negative ¹⁸F-FMISO uptake. ¹⁸F-FMISO uptake was observed in all high-grade gliomas but not in low-grade gliomas. A significant relationship was found between ¹⁸F-FDG or ¹⁸F-FMISO uptake and expression of VEGF-R1 and Ki67 expression. Other immunohistochemical markers demonstrated a trend toward increased uptake but none was significant. Conclusion: ¹⁸F-FMISO PET provides a noninvasive assessment of hypoxia in glioma and was prognostic for treatment outcomes in the majority of patients.¹⁸F-FMISO PET may have a role not only in directing patients toward targeted hypoxic therapies but also in monitoring response to such therapies.

Key Words: PET • tumor hypoxia • glioma

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