Discrimination between low-grade oligodendrogliomas and diffuse astrocytoma with the aid of 11C-methionine positron emission tomography

Clinical article

Restricted access

Object

The diagnostic usefulness of 11C-methionine PET scans in gliomas is still controversial. The authors investigated the clinical significance of 11C-methionine PET findings in preoperative diagnosis of histological type and grade.

Methods

The tissue uptake of 11C-methionine was assessed using PET in 70 patients with histologically confirmed intracerebral gliomas. The ratio of maximum standard uptake values in tumor areas to the mean standard uptake values in the contralateral normal brain tissue (tumor/normal tissue [T/N] ratio) was calculated and correlated with tumor type, histological grade, contrast enhancement on MR imaging, Ki 67 labeling index, and 1p/19q status.

Results

The T/N ratio was significantly increased as tumor grade advanced in astrocytic tumors (WHO Grade II vs Grade III, p = 0.0011; Grade III vs Grade IV, p = 0.0007). Among Grade II gliomas, the mean T/N ratio was significantly higher in oligodendroglial tumors than in diffuse astrocytomas (DAs) (p < 0.0001). All T/N ratios for oligodendroglial tumors were ≥ 1.46, and those for DA were consistently < 1.46, with the exception of 2 cases of gemistocytic astrocytoma. The Ki 67 labeling index significantly correlated with T/N ratio in astrocytic tumors, but not in oligodendrogliomas. Oligodendroglial tumors without 1p/19q deletion had a significantly higher T/N ratio than those with the codeletion. In combination with Gd-enhanced MR imaging, 67% of nonenhanced tumors with a T/N ratio of ≥ 1.46 were proved to be Grade II oligodendrogliomas.

Conclusions

These results clearly show that 11C-methionine PET T/N ratios in Grade II oligodendrogliomas were higher than those in DAs independently of their proliferative activity. This information contributes to preoperative differential diagnoses of histological type, especially in suspected low-grade gliomas.

Abbreviations used in this paper: DA = diffuse astrocytoma; FISH = fluorescence in situ hybridization; LI = labeling index; ROI = region of interest; SUV = standard uptake value; T/N = tumor/normal tissue.

Article Information

Address correspondence to: Yasuo Iwadate, M.D., Ph.D., Department of Neurological Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan. email: iwadatey@faculty.chiba-u.jp.

Please include this information when citing this paper: published online January 7, 2011; DOI: 10.3171/2010.11.JNS10553.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Scatter diagram of methionine SUVs for T/N ratios in astrocytic tumors. The mean SUV T/N ratio was 1.06 ± 0.26 for Grade II astrocytoma, 2.43 ± 0.96 for anaplastic astrocytoma (Grade III), and 3.81 ± 1.08 for glioblastoma (Grade IV). The T/N ratio increased significantly in proportion to advancing tumor grade (p = 0.0011 between Grades II and III, p = 0.0007 between Grades III and IV; Fisher protected least significant difference analysis).

  • View in gallery

    Scatter diagram of methionine SUVs for T/N ratios in oligodendrogliomas. The mean SUV T/N ratio was 2.38 ± 0.74 for Grade II oligodendrogliomas and 2.86 ± 1.24 for anaplastic oligodendrogliomas (Grade III). There was no significant difference between Grades II and III (p = 0.101, unpaired t-test).

  • View in gallery

    Representative images obtained in patients with DA (images were obtained in a different patient in each row). Axial MR images demonstrate nonenhancing tumors (A, D, and G) with signal-hyperintense areas on T2-weighted imaging (B, E, and H). The 11C-methionine PET scans (C, F, and I) show relatively low uptake levels in the tumor areas.

  • View in gallery

    Representative images obtained in patients with Grade II oligodendroglial tumor (images were obtained in a different patient in each row). Axial MR images demonstrate nonenhancing tumors (A, D, and G) with signal-hyperintense areas on T2-weighted imaging (B, E, and H), resembling the imaging features for DA (see Fig. 3). In contrast, 11C-methionine PET scans (C, F, and I) show high uptake levels in the tumor areas.

  • View in gallery

    Scatter diagram demonstrating differences in methionine SUVs of the T/N ratio depending on histological type as either Grade II astrocytoma or oligodendroglioma. The mean SUV T/N ratio was significantly higher in Grade II oligodendrogliomas than in Grade II astrocytoma (2.38 ± 0.74 and 1.06 ± 0.26, respectively; p < 0.0001, unpaired t-test). The horizontal line shows a cutoff threshold of 1.46 for the T/N ratio. All oligodendroglial tumors exist above this line, whereas all nongemistocytic DAs are under this threshold.

  • View in gallery

    Correlation of the methionine SUVs for T/N ratios with Ki 67 LI. Left: The T/N ratio shows a positive correlation with Ki 67 in 20 astrocytic tumors (p = 0.0129). Right: The T/N ratio shows no correlation with Ki 67 LI in 19 oligodendrogliomas (p = 0.18).

  • View in gallery

    Scatter diagram demonstrating differences in methionine SUVs of T/N ratio depending on 1p/19q status in oligodendrogliomas. The mean SUV T/N ratio was significantly higher in oligodendroglial tumors without 1p/19q deletion than in those with 1p/19q deletion (3.25 ± 0.79 and 2.35 ± 0.78, respectively; p = 0.0173, unpaired t-test).

References

  • 1

    Bading JRKan-Mitchell JConti PS: System A amino acid transport in cultured human tumor cells: implications for tumor imaging with PET. Nucl Med Biol 23:7797861996

    • Search Google Scholar
    • Export Citation
  • 2

    Behin AHoang-Xuan KCarpentier AFDelattre JY: Primary brain tumours in adults. Lancet 361:3233312003

  • 3

    Braun VDempf SWeller RReske SNSchachenmayr WRichter HP: Cranial neuronavigation with direct integration of (11)C methionine positron emission tomography (PET) data—results of a pilot study in 32 surgical cases. Acta Neurochir (Wien) 144:7777822002

    • Search Google Scholar
    • Export Citation
  • 4

    Bromberg JECvan den Bent MJ: Oligodendrogliomas: molecular biology and treatment. Oncologist 14:1551632009

  • 5

    Ceyssens SVan Laere Kde Groot TGoffin JBormans GMortelmans L: [11C]methionine PET, histopathology, and survival in primary brain tumors and recurrence. AJNR Am J Neuroradiol 27:143214372006

    • Search Google Scholar
    • Export Citation
  • 6

    Chung JKKim YKKim SKLee YJPaek SYeo JS: Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET. Eur J Nucl Med Mol Imaging 29:1761822002

    • Search Google Scholar
    • Export Citation
  • 7

    De Witte OGoldberg IWikler DRorive SDamhaut PMonclus M: Positron emission tomography with injection of methionine as a prognostic factor in glioma. J Neurosurg 95:7467502001

    • Search Google Scholar
    • Export Citation
  • 8

    Durand KSGuillaudeau AWeinbreck NDeArmas RRobert SChaunavel A: 1p19q LOH patterns and expression of p53 and Olig2 in gliomas: relation with histological types and prognosis. Mod Pathol 23:6196282010

    • Search Google Scholar
    • Export Citation
  • 9

    Gan HKRosenthal MADowling AKalnins RAlgar EWong N: A phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors. Neuro Oncol 12:5005072010

    • Search Google Scholar
    • Export Citation
  • 10

    Giannini CBurger PCBerkey BACairncross JGJenkins RBMehta M: Anaplastic oligodendroglial tumors: refining the correlation among histopathology, 1p 19q deletion and clinical outcome in Intergroup Radiation Therapy Oncology Group Trial 9402. Brain Pathol 18:3603692008

    • Search Google Scholar
    • Export Citation
  • 11

    Goldman SLevivier MPirotte BBrucher JMWikler DDamhaut P: Regional glucose metabolism and histopathology of gliomas. A study based on positron emission tomography-guided stereotactic biopsy. Cancer 78:109811061996

    • Search Google Scholar
    • Export Citation
  • 12

    Higuchi YIwadate YYamaura A: Treatment of low-grade oligodendroglial tumors without radiotherapy. Neurology 63:238423862004

  • 13

    Iuchi TIwadate YNamba HOsato KSaeki NYamaura A: Glucose and methionine uptake and proliferative activity in meningiomas. Neurol Res 21:6406441999

    • Search Google Scholar
    • Export Citation
  • 14

    Iwadate YSakaida THiwasa TNagai YIshikura HTakiguchi M: Molecular classification and survival prediction in human gliomas based on proteome analysis. Cancer Res 64:249625012004

    • Search Google Scholar
    • Export Citation
  • 15

    Jager PLVaalburg WPruim Jde Vries EGLangen KJPiers DA: Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med 42:4324452001

    • Search Google Scholar
    • Export Citation
  • 16

    Kaschten BStevenaert ASadzot BDeprez MDegueldre CDel Fiore G: Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med 39:7787851998

    • Search Google Scholar
    • Export Citation
  • 17

    Kato TShinoda JNakayama NMiwa KOkumura AYano H: Metabolic assessment of gliomas using 11C-methionine, [18F] fluorodeoxyglucose, and 11C-choline positron-emission tomography. AJNR Am J Neuroradiol 29:117611822008

    • Search Google Scholar
    • Export Citation
  • 18

    Kim SChung JKIm SHJeong JMLee DSKim DG: 11C-methionine PET as a prognostic marker in patients with glioma: comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging 32:52592005

    • Search Google Scholar
    • Export Citation
  • 19

    Kondziolka DLunsford LDMartinez AJ: Unreliability of contemporary neurodiagnostic imaging in evaluating suspected adult supratentorial (low-grade) astrocytoma. J Neurosurg 79:5335361993

    • Search Google Scholar
    • Export Citation
  • 20

    Kracht LWFriese MHerholz KSchroeder RBauer BJacobs A: 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 30:8688732003

    • Search Google Scholar
    • Export Citation
  • 21

    Kracht LWMiletic HBusch SJacobs AHVoges JHoevels M: Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res 10:716371702004

    • Search Google Scholar
    • Export Citation
  • 22

    Kubota K: From tumor biology to clinical PET: a review of positron emission tomography (PET) in oncology. Ann Nucl Med 15:4714862001

    • Search Google Scholar
    • Export Citation
  • 23

    Lebrun CFontaine DBourg VRamaioli AChanalet SVandenbos F: Treatment of newly diagnosed symptomatic pure low-grade oligodendrogliomas with PCV chemotherapy. Eur J Neurol 14:3913982007

    • Search Google Scholar
    • Export Citation
  • 24

    Nariai TTanaka YWakimoto HAoyagi MTamaki MIshiwata K: Usefulness of L-[methyl-11C] methionine–positron emission tomography as a biological monitoring tool in the treatment of glioma. J Neurosurg 103:4985072005

    • Search Google Scholar
    • Export Citation
  • 25

    Ogawa TKanno IHatazawa JInugami AFujita HShimosegawa E: Methionine PET for follow-up of radiation therapy of primary lymphoma of the brain. Radiographics 14:1011101994

    • Search Google Scholar
    • Export Citation
  • 26

    Okita YKinoshita MGoto TKagawa NKishima HShimosegawa E: (11)C-methionine uptake correlates with tumor cell density rather than with microvessel density in glioma: a stereotactic image-histology comparison. Neuroimage 49:297729822010

    • Search Google Scholar
    • Export Citation
  • 27

    Ribom DEriksson AHartman MEngler HNilsson ALångström B: Positron emission tomography (11)Cmethionine and survival in patients with low-grade gliomas. Cancer 92:154115492001

    • Search Google Scholar
    • Export Citation
  • 28

    Singhal TNarayanan TKJain VMukherjee JMantil J: 11CL-methionine positron emission tomography in the clinical management of cerebral gliomas. Mol Imaging Biol 10:1182008

    • Search Google Scholar
    • Export Citation
  • 29

    Souba WWPacitti AJ: How amino acids get into cells: mechanisms, models, menus, and mediators. JPEN J Parenter Enteral Nutr 16:5695781992

    • Search Google Scholar
    • Export Citation
  • 30

    Wessels PHWeber WERaven GRamaekers FCHopman AHTwijnstra A: Supratentorial grade II astrocytoma: biological features and clinical course. Lancet Neurol 2:3954032003

    • Search Google Scholar
    • Export Citation

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 193 193 15
Full Text Views 159 136 4
PDF Downloads 91 70 3
EPUB Downloads 0 0 0

PubMed

Google Scholar