11C-methionine (MET) and 18F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma
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The purpose of this prospective study was to clarify the individual and combined role of l-methyl-11C-methionine-positron emission tomography (MET-PET) and 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grades.
Materials and methods
Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake (SUVmax), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining.
On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false negative on FLT-PET. Although the difference of MET SUVmax and T/N ratio between grades II and IV gliomas was statistically significant (P < 0.001), there was a significant overlap of MET uptake in the tumors. The difference of MET SUVmax and T/N ratio between grades II and III gliomas was not statistically significant. Low-grade gliomas with oligodendroglial components had relatively high MET uptake. The difference of FLT SUVmax and T/N ratio between grades III and IV gliomas was statistically significant (P < 0.01). Again, the difference of FLT SUVmax and T/N ratio between grades II and III gliomas was not statistically significant. Grade III gliomas with non-contrast enhancement on MR images had very low FLT uptake. In 18 patients who underwent PET examination with both tracers, a significant but relatively weak correlation was observed between the individual SUVmax of MET and FLT (r = 0.54, P < 0.05) and T/N ratio of MET and FLT (r = 0.56, P < 0.05). Total FLT uptake in the tumor had a higher correlation (r = 0.89, P < 0.001) with Ki-67 proliferation index than MET uptake (r = 0.49, P < 0.01).
PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas. However, there is no complimentary information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas. FLT-PET seems to be superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grades.
- Herholz K, Hölzer T, Bauer B, Schröder R, Voges J, Ernestus R-I, Mendoza G, Weber-Luxenburger G, Löttgen J, Thiel A, Wienhard K, Heiss W-D. 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology 1998;50:1316–22.
- Ceyssens S, Van Laere K, de Groot T, Goffin J, Bormans G, Mortelmans L. [11C]methionine PET, histopathology, and survival in primary brain tumors and recurrence. AJNRAm J Neuroradiol 2006;27:1432–7.
- Kaschten B, Stevenaert A, Sadzot B, Deprez M, Degueldre C, Fiore GD, Luxen A, Reznik M. Preoperative evaluation of 54 gliomas by PET with fluorine-18- fluorodeoxyglucose and /or carbon-11-methinine. J Nucl Med 1998;39:778–85.
- Nariai T, Tanaka Y, Wakimoto H, Aoyagi M, Tamaki M, Ishikawa K, Senda M, Ishii K, Hirakawa K, Ohno K. Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma. J Neurosurg 2005;103:498–507.
- Ribom D, Eriksson A, Hartman M, Engler H, Nilsson A, Långström B, Bolander H, Bergström M, Smits A. Positron emission tomography 11C-methionine and survival in patients with low-grade gliomas. Cancer 2001;92:2541–1549. CrossRef
- Van Laere K, Ceyssens S, Van Calenbergh F, de Groot T, Menten J, Falmen P, Bormans G, Mortelmans L. Direct comparison of 18F-FDG and 11C-methionine PET in suspected recurrence of glioma: sensitivity, inter-observer variability and prognostic value. Eur J Nucl Med Mol Imaging 2005;32:39–51. CrossRef
- Ribom D, Engler H, Blomquist E, Smits A. Potential significance of 11C- methionine PET as a marker for the radiosensitivity of low grade gliomas. Eur J Nucl Med 2002;29:632–40. CrossRef
- Nuutinen J, Sonninen P, Lehikoinen P, Sutinen E, Valavaara R, Eronen E, Norrgård S, Kulmala J, Teräs M, Minn H. Radiotherapy treatment planning and long-term follow-up with [11C]methionine PET in patients with low-grade astrocytoma. Int J Radiat Oncol Biol Phys 2000;48:43–52. CrossRef
- Galldiks N, Kracht LW, Burghaus L, Thomas A, Jacobs AH, Heiss WD, Herholz K. Use of 11C-methionine PET to monitor the effects of temozolomide chemotherapy in malignant gliomas. Eur J Nucl Med Mol Imaging 2006;33:516–24. CrossRef
- Sonoda Y, Kumabe T, Takahashi T, Shirane R, Yoshimoto T. Clinical usefulness of 11C-methinine PET and 201Tl SPECT for differentiation of recurrent glioma from radiation necrosis. Neurol Med Chir (Tokyo) 1998;38:342–8. CrossRef
- Tsuyuguchi N, Takami T, Sunada I, Iwai Y, Yamanaka K, Tanaka K, Nishikawa M, Ohata K, Torii K, Morino M, Nishio A, Hara M. Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery -in malignant glioma-. Ann Nucl Med 2004;18:291–6.
- Ishii K, Ogawa T, Hatazawa J, Kanno I, Inugami A, Fujita H, Shimosegawa E, Murakami M, Okudera T, Uemura K. High l-methyl-[11C]methionine uptake in brain abscess: a PET study. J Comput Assist Tomogr 1993;17:660–1. CrossRef
- Nakagawa M, Nuwabara Y, Sasaki M, Koga H, Chen T, Kaneko O, Hayashi K, Morioka T, Masuda K. 11C-methionine uptake in cerebrovascular disease: a comparison with 18F-fDG PET and 99mTc-HMPOA SPECT. Ann Nucl Med 2002;16:207–11.
- Chen W, Cloughesy T, Kamdar N, Satyamurthy N, Bergsneider M, Liau L, Mischel P, Czernin J, Phelps ME, Silverman DHS. Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG. J Nucl Med 2005;46:945–52.
- Choi SJ, Kim JS, Kim JH, Oh SJ, Lee JG, Kim CJ, Ra YS, Yeo JS, Ryu JS, Moon DH. [18F]3’-deoxy-3’-fluorothymidine PET for the diagnosis and grading of brain tumors. Eur J Nucl Med Mol Imaging 2005;32:653–9. CrossRef
- Saga T, Kawashima H, Araki N, Takahashi JA, Nakashima Y, Higashi T, Oya N, Murai T, Hojo M, Hashimoto N, Manabe T, Hiraoka M, Togashi K. Evaluation of primary brain tumors with FLT-PET: usefulness and limitations. Clin Nucl Med 2006;31:774–80. CrossRef
- Shiels AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, Obradovich JE, Muzik O, Mangner TJ. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 1998;4:1334–36. CrossRef
- Been LB, Suumeijer AJH, Cobben DCP, Jager PL, Hoekstra HJ, Elsinga PH. [18F]FLT-PET in oncology: current status and opportunities. Eur J Nucl Med Mol Imaging 2004;31:1659–72. CrossRef
- Jacobs AH, Thomas A, Kracht LW, Li H, Dittmar C, Garlip G, Galldiks N, Klein JC, Sobesky J, Hilker R, Vollmar S, Herholz K, Wienhard K, Heiss W-D. 18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors. J Nucl Med 2005;46:1948–58.
- Chen W, Delaloye S, Silverman DHS, Geist C, Czernin J, Sayre J, Satyamurthy N, Pope W, Lai A, Phelps ME, Cloughesy T. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol 2007;25:4714–21. CrossRef
- Cao Y, Tsien CI, Shen Z, Tatro DS, Ten Haken R, Kessier ML, Chenevert TL, Lawrence TS. Use of magnetic resonance imaging to assess blood–brain/blood–gliomas barrier opening during conformal radiotherapy. J Clin Oncol 2005;23:4127–36. CrossRef
- Yuan H, Gaber MW, Boyd K, Wilson CM, Kiani MF, Merchant TE. Effects of fractionated radiation on the brain vasculature in a murine model: blood–brain barrier permeability, astrocyte proliferation, and ultrastructural changes. Int J Radiat Oncol Biol Phys 2006;66:860–6.
- Machulla HJ, Blocher A, Kuntzsch M, Grierson JR. Simplified labeling approach for synthesizing 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT). J Radioanal Nucl Chem 2000;24:843–6. CrossRef
- Ishiwata K, Ido T, Vaalburg W. Increased amounts of d-enantiomer dependent on alkaline concentration in the synthesis of l-[methyl-11C]methionine. Appl Radiat Isot 1998;39:311–4.
- Ogawa T, Inugami A, Hatazawa J, Kannno I, Murakami M, Yasui N, Mineura K, Uemura K. Clinical positron emission tomography for brain tumors: comparison of fludeoxyglucose F 18 and L-methyl-11C-methinone. AJNR Am J Neuroradiol 1996;17:345–53.
- Borbély K, Nyáry I, Tóth M, Ericson K, Gulyás B. Optimization of semi-quantification in metabolic PET studies with 18F-fluorodeoxyglucose and 11C-methionine in the determination of malignancy of gliomas. J Neurol Sci 2006;246:85–94. CrossRef
- Ogawa T, Hatazawa J, Inugami A, Murakami M, Fujita H, Shimosegawa E, Noguchi K, Okudera T, Kanno I, Uemura K, Hadeishi H, Sasajima T. Carbon-11-methinone PET evaluation of intracerebral hematoma: distinguishing neoplastic from non-neoplastic hematoma. J Nucl Med 1995;36:2175–9.
- Kim S, Chung J-K, Im S-H, Jeong JM, Lee DS, Kim DG, Jung HW, Lee MC. 11C-methionine PET as a prognostic marker in patients with glioma: comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging 2005;32:52–9. CrossRef
- Sato N, Suzuki M, Kuwata N, Kuroda K, Wada T, Beppu T, Sera K, Sasaki T, Ogawa A. Evaluation of the malignancy of glioma using 11C-methionine positron emission tomography and proliferating cell nuclear antigen staining. Neurosurg Rev 1999;22:210–4. CrossRef
- Kracht LW, Friese M, Herholz K, Schroeder R, Bauer B, Jacobs A, Heiss W-D. Methyl-[11C]-L-methionine uptake as measured by positron emission tomography correlates to microvessel density in patients with glioma. Eur J Nucl Med Mol Imaging 2003;30:868–73.
- Derlon J-M, Petit-Taboué M-C, Chapon F, Beaudouin V, Noël M-H, Creveuil C, Courtheoux P, Houtteville J-P. The in vivo metabolic pattern of low-grade brain gliomas: a positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-l-methylmethionine. Neurosurgery 1997;40:276–88. CrossRef
- De Witte O, Goldberg I, Wikler D, Rorive S, Damhaut P, Monclus M, Salmon I, Brotchi J, Goldman S. Positron emission tomography with injection of methionine as a prognostic factor in glioma. J Neurosurg 2001;95:746–50. CrossRef
- Miwa K, Shinoda J, Yano H, Okumura A, Iwama T, Nakahashi T, Sakai N. Discrepancy between lesion distributions on methionine PET and MR images in patients with glioblastoma multiforme: insight from a PET and MR fusion image study. J Neurol Neurosurg Psychiatry 2004;75:1457–62. CrossRef
- Toyohara J, Waki A, Takamatsu S, Yonekura Y, Magata Y, Fujibayashi Y. Basis of FLT as a cell proliferation marker: comparative uptake studies with [3H]thymidine and [3H]arabinothymidine, and cell-analysis in 22 asynchronously growing tumor cell lines. Nucl Med Biol 2002;29:281–7. CrossRef
- Schwartz JL, Tamura Y, Jordan R, Grierson JR, Hrohn KA. Monitoring tumor cell proliferation by targeting DNA synthetic processes with thymidine and thymidine analogs. J Nucl Med 2003;44:2027–32.
- Muzi M, Spence AM, O’Sullivan F, Mankoff DA, Wells JM, Grierson JR, Link JM, Krohn KA. Kinetic analysis of 3′-deoxy-3′-18F-fluorothymidine in patients with gliomas. J Nucl Med 2006;47:1612–21.
- 11C-methionine (MET) and 18F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma
European Journal of Nuclear Medicine and Molecular Imaging
Volume 35, Issue 11 , pp 2009-2017
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- Positron emission tomography
- Cellular proliferation
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- Author Affiliations
- 1. Department of Neurological Surgery, Kagawa University School of Medicine, 1750-1 Miki-cho, Kita-gun, Kagawa, 761-0793, Japan
- 2. Department of Radiology, Kagawa University School of Medicine, Kagawa, Japan
- 3. Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan