We investigated the sensitivity and specificity of [11C]-methionine positron emission tomography ([11C]-MET PET) in the management of glioma patients. We retrospectively analysed data from 53 patients with primary gliomas (16 low grade astrocytomas, 15 anaplastic astrocytomas and 22 glioblastomas) and Karnofsky Performance Status (KPS) > 70. Patients underwent [11C]-MET PET scans ( ) and parallel contrast-enhanced MRI ( ) and/or CT ( ) controls. In low grade glioma patients, MRI or CT findings associated with [11C]-MET PET additional data allowed discrimination residual disease from postsurgical changes in 96.22% of these cases. [11C]-MET PET early allowed detection of malignant progression from low grade to anaplastic astrocytoma with high sensitivity (91.56%) and specificity (95.18%). In anaplastic astrocytomas, we registered high sensitivity (93.97%) and specificity (95.18%) in the postoperative imaging and during the followup of these patients. In GBM patients, CT and/or MRI scans with additional [11C]-MET PET data registered a sensitivity of 96.92% in the postsurgical evaluation and in the tumour assessment during temozolomide therapy. A significant correlation was found between [11C]-MET mean uptake index and histologic grading ( ). These findings support the notion that complementary information derived from [11C]-MET PET may be helpful in postoperative and successive tumor assessment of glioma patients. 1. Introduction The therapeutic approach to glioma patients remains a major challenge in clinical neurooncology, mainly for the inefficiency of the conventional instrumental methods to assess the response to the different therapeutic tools. In fact, an adequate imaging may affect the assessment of an objective response rate and the determination of the progression-free survival, thus influencing the therapeutic course of glioma patients. In neuroradiology, contrast enhancement reflects blood-brain barrier damage regions and it is considered an indirect marker for active tumor tissue. However, MRI contrast enhancement often does not adequately differentiate viable tumor tissue from necrosis induced by therapy or occurring spontaneously during tumour progression [1]. Furthermore, contrast enhancement may be confused by dexamethasone, which reduces the uptake of contrast agents [2]. Positron emission tomography (PET) may improve the management of malignant glioma by identifying areas of increased metabolic activity beyond the area of contrast enhancement on MRI, which may correspond to the areas at highest risk of recurrence. Moreover, PET imaging
References
[1]
M. J. van den Bent, M. A. Vogelbaum, P. Y. Wen, D. R. Macdonald, and S. M. Chang, “End point assessment in gliomas: novel treatments limit usefulness of classical Macdonald's criteria,” Journal of Clinical Oncology, vol. 27, no. 18, pp. 2905–2908, 2009.
[2]
L. ？Stergaard, F. H. Hochberg, J. D. Rabinov et al., “Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors,” Journal of Neurosurgery, vol. 90, no. 2, pp. 300–305, 1999.
[3]
T. Kato, J. Shinoda, N. Nakayama et al., “Metabolic assessment of gliomas using 11C-methionine, [18F] fluorodeoxyglucose, and 11C-choline positron-emission tomography,” American Journal of Neuroradiology, vol. 29, no. 6, pp. 1176–1182, 2008.
[4]
R. Stupp, M. E. Hegi, W. P. Mason et al., “Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial,” The Lancet Oncology, vol. 10, no. 5, pp. 459–466, 2009.
[5]
D. N. Louis, H. Ohgaki, O. D. Wiestler et al., “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathologica, vol. 114, no. 5, pp. 97–109, 2007.
[6]
D. R. Macdonald, T. L. Cascino, S. C. Schold Jr., and J. G. Cairncross, “Response criteria for phase II studies of supratentorial malignant glioma,” Journal of Clinical Oncology, vol. 8, no. 7, pp. 1277–1280, 1990.
[7]
E. Kaplan and P. Meier, “Non parametric estimation for incomplete observation,” Journal of the American Statistical Association, vol. 53, no. 282, pp. 457–481, 1958.
[8]
J. K. Chung, Y. Kim, S. K. Kim et al., “Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET,” European Journal of Nuclear Medicine, vol. 29, no. 2, pp. 176–182, 2002.
[9]
N. Sato, M. Suzuki, N. Kuwata et al., “Evaluation of the malignancy of glioma using 11C-methionine positron emission tomography and proliferating cell nuclear antigen staining,” Neurosurgical Review, vol. 22, no. 4, pp. 210–214, 1999.
[10]
J. M. Derlon, C. Bourdet, P. Bustany et al., “[11C]L-Methionine uptake in gliomas,” Neurosurgery, vol. 25, no. 5, pp. 720–728, 1989.
[11]
L. W. Kracht, M. Friese, K. Herholz et al., “Methyl-[11C]-L-methionine uptake as measured by positron emission tomography correlates to microvessel density in patients with glioma,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 30, no. 6, pp. 868–873, 2003.
[12]
A. F. Thornton Jr., T. J. Hegarty, H. R. K. Ten et al., “Three dimensional treatment planning of astrocytomas: a dosimetry study of cerebral irradiation,” International Journal of Radiation Oncology * Biology * Physics, vol. 20, no. 6, pp. 1309–1315, 1991.
[13]
A. H. Jacobs, A. Winkeler, C. Dittmar et al., “Molecular and functional imaging technology for the development of efficient treatment strategies for gliomas,” Technology in Cancer Research and Treatment, vol. 1, no. 3, pp. 187–204, 2002.
[14]
A. L. Grosu, W. A. Weber, E. Riedel et al., “L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy,” International Journal of Radiation Oncology Biology Physics, vol. 63, no. 1, pp. 64–74, 2005.
[15]
T. Ogawa, I. Kanno, F. Shishido et al., “Clinical value of PET with 18F-fluorodeoxyglucose and L-methyl-11C-methionine for diagnosis of recurrent brain tumor and radiation injury,” Acta Radiologica, vol. 32, no. 3, pp. 197–202, 1991.
[16]
K. Mineura, T. Sasajima, M. Kowada, Y. Uesaka, and F. Shishido, “Innovative approach in the diagnosis of gliomatosis cerebri using carbon-11-L-methionine positron emission tomography,” Journal of Nuclear Medicine, vol. 32, no. 4, pp. 726–728, 1991.
[17]
N. Galldiks, V. Dunkl, L. W. Kracht et al., “Volumetry of [11C]-methionine positron emission tomographic uptake as a prognostic marker before treatment of patients with malignant glioma,” Molecular Imaging, vol. 11, pp. 516–527, 2012.
[18]
M. Matsuo, K. Miwa, O. Tanaka et al., “Impact of [11C]methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning,” International Journal of Radiation Oncology Biology Physics, vol. 82, no. 1, pp. 83–89, 2012.
[19]
Y. Terakawa, N. Tsuyuguchi, Y. Iwai et al., “Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy,” Journal of Nuclear Medicine, vol. 49, no. 5, pp. 694–699, 2008.
