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Methyl-L-¹¹C-Methionine PET as a Diagnostic Marker for Malignant Progression in Patients with Glioma

¹ Max Planck Institute for Neurological Research with Klaus Joachim Zülch Laboratories, Cologne, Germany; ² Center for Molecular Medicine, University of Cologne, Cologne, Germany; ³ Department of Neuropathology, University of Cologne, Cologne, Germany; ⁴ University of Manchester, Manchester, United Kingdom; ⁵ Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany; ⁶ Department of Biomedicine, University of Bergen, Bergen, Norway; ⁷ Department of Pathology, Haukeland University Hospital, Bergen, Norway; ⁸ Klinikum Fulda, Fulda, Germany; and ⁹ European Institute of Molecular Imaging–EIMI, University of Muenster, Muenster, Germany

Correspondence: For correspondence or reprints contact: Andreas H. Jacobs, Laboratory for Gene Therapy and Molecular Imaging, MPI for Neurological Research, Gleuelerstrasse 50, 50931 Cologne, Germany. E-mail: Andreas.Jacobs{at}nf.mpg.de

Methyl-L-¹¹C-methionine (¹¹C-MET) PET has been shown to detect brain tumors with a high sensitivity and specificity. In this study, we investigated the potential of ¹¹C-MET PET to noninvasively detect tumor progression in patients with gliomas. Moreover, we analyzed the relationship between changes in ¹¹C-MET uptake on PET and changes in various molecular immunohistochemical markers during progression of gliomas. Methods: Twenty-four patients with histologically proven glioma were investigated repeatedly with ¹¹C-MET PET. ¹¹C-MET uptake was determined for a circular region of interest. Histologic and molecular analyses for tumor progression were performed after open surgery and stereotactic biopsy, respectively. Results: In patients with malignant progression, the mean increase in ¹¹C-MET uptake was 54.4% (SD, 45.5%; range, 3.1%–162.2%), whereas in patients without a change in tumor grade, mean ¹¹C-MET uptake did not significantly change (3.9%; SD, 13.7%; range, –24.4% to 26.3%). The difference in the change in ¹¹C-MET uptake between the group with malignant progression and the group without malignant progression was highly significant (P < 0.001). Receiver-operating-curve analysis revealed a sensitivity of 90% and a specificity of 92.3% for the detection of malignant transformation by an increase in ¹¹C-MET uptake of more than 14.6%. Increased ¹¹C-MET uptake of more than 14.6% was indicative of malignant progression in all but 3 leave-one-out iterations. A detailed immunohistochemical analysis demonstrated a significant correlation between changes in ¹¹C-MET uptake and the expression of vascular endothelial growth factor. Conclusion: These data suggest that ¹¹C-MET-PET represents a noninvasive method to detect malignant progression in patients with gliomas. Moreover, the increase in ¹¹C-MET uptake during malignant progression is reflected by an increase in angiogenesis-promoting markers as vascular endothelial growth factor.

Key Words: [¹¹C]MET • PET • gliomas • malignant progression • angiogenesis

^* Contributed equally to this work.

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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