Skip to main content

Advertisement

SpringerLink
Log in

Met-PET uptake index for total tumor resection: identification of 11C-methionine uptake index as a goal for total tumor resection including infiltrating tumor cells in glioblastoma

  • Original Article
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Glioblastoma multiforme (GBM) is largely due to glioma stem cells (GSCs) that escape from total resection of gadolinium (Gd)-enhanced tumor on MRI. The aim of this study is to identify the imaging requirements for maximum resection of GBM with infiltrating GSCs. We investigated the relationship of tumor imaging volume between MRI and 11C-methionine (Met)-PET and also the relationship between Met uptake index and tumor activity. In ten patients, tumor-to-contralateral normal brain tissue ratio (TNR) was calculated to evaluate metabolic activity of Met uptake areas which were divided into five subareas by the degrees of TNR. In each GBM, tumor tissue was obtained from subareas showing the positive Met uptake. Immunohistochemistry was performed to examine the tumor proliferative activity and existence of GSCs. In all patients, the volume of Met uptake area at TNR ≦ 1.4 was larger than that of the Gd-enhanced area. The Met uptake area at TNR 1.4 beyond the Gd-enhanced tumor was much wider in high invasiveness–type GBMs than in those of low invasiveness type, and survival was much shorter in the former than the latter types. Immunohistochemistry revealed the existence of GSCs in the area showing Met uptake at TNR 1.4 and no Gd enhancement. Areas at TNR > 1.4 included active tumor cells with relatively high Ki-67 labeling index. In addition, it was demonstrated that GSCs could exist beyond the border of Gd-enhanced tumor. Therefore, to obtain maximum resection of GBMs, including infiltrating GSCs, aggressive surgical excision that includes the Met-positive area at TNR 1.4 should be considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Arbizu J, Tejada S, Marti-Climent JM, Diez-Valle R, Prieto E, Quincoces G, Vigil C, Idoate MA, Zubieta JL, Peñuelas I, Richter JA (2012) Quantitative volumetric analysis of gliomas with sequential MRI and 11C-methionine PET assessment: patterns of integration in therapy planning. Eur J Nucl Med Mol Imaging 39(5):771–781

    Article  Google Scholar 

  2. Della Puppa A, Lombardi G, Rossetto M, Rustemi O, Berti F, Cecchin D, Gardiman MP, Rolma G, Persano L, Zagonel V, Scienza R (2017) Outcome of patients affected by newly diagnosed glioblastoma undergoing surgery assisted by 5-aminolevulinic acid guided resection followed by BCNU wafers implantation: a 3-year follow-up. J Neuro-Oncol 131(2):331–340

    Article  CAS  Google Scholar 

  3. Donovan LK, Potter NE, Warr T, Pilkington GJ (2012) A prominin-1-rich pediatric glioblastoma: biologic behavior is determined by oxygen tension-modulated CD133 expression but not accompanied by underlying molecular profiles. Transl Oncol 5(3):141–154

    Article  Google Scholar 

  4. Galldiks N, Ullrich R, Schroeter M, Fink GR, Jacobs AH, Kracht LW (2010) Volumetry of [(11)C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme. Eur J Nucl Med Mol Imaging 37(1):84–92

    Article  Google Scholar 

  5. Giese A, Kucinski T, Knopp U, Goldbrunner R, Hamel W, Mehdorn HM, Tonn JC, Hilt D, Westphal M (2004) Pattern of recurrence following local chemotherapy with biodegradable carmustine (BCNU) implants in patients with glioblastoma. J Neuro-Oncol 66(3):351–360

    Article  Google Scholar 

  6. Grosu AL, Weber WA, Riedel E, Jeremic B, Nieder C, Franz M, Gumprecht H, Jaeger R, Schwaiger M, Molls M (2005) L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. Int J Radiat Oncol Biol Phys 63(1):64–74

    Article  CAS  Google Scholar 

  7. Jacobs AH, Winkler A, Dittmar C, Gossman A, Deckert M, Kracht L, Thiel A, Garlip G, Hilker R, Sobesky J, Vollmar S, Kummer C, Graf R, Voges J, Wienhard K, Herholz K, Heiss WD (2002) Molecular and functional imaging technology for the development of efficient treatment strategies for gliomas. Technol Cancer Res Treat 1(3):187–204

    Article  CAS  Google Scholar 

  8. Kobayashi K, Hirata K, Yamaguchi S, Manabe O, Terasaka S, Kobayashi H, Shiga T, Hattori N, Tanaka S, Kuge Y, Tamaki N (2015) Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients. Eur J Nucl Med Mol Imaging 42(7):1071–1080

    Article  CAS  Google Scholar 

  9. Kracht LW, Miletic H, Busch S, Jacobs AH, Voges J, Hoevels M, Klein JC, Herholz K, Heiss WD (2004) Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res 10(21):7163–7170

    Article  CAS  Google Scholar 

  10. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95(2):190–198

    Article  CAS  Google Scholar 

  11. Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE, Hjelmeland AB, Rich JN (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15(6):501–513

    Article  CAS  Google Scholar 

  12. Lucas JT Jr, Serrano N, Kim H, Li X, Snyder SE, Hwang S, Li Y, Hua CH, Broniscer A, Merchant TE, Shulkin BL (2017) 11C-Methionine positron emission tomography delineates non-contrast enhancing tumor regions at high risk for recurrence in pediatric high-grade glioma. J Neuro-Oncol 132(1):163–170

    Article  Google Scholar 

  13. Matsuo M, Miwa K, Tanaka O, Shinoda J, Nishibori H, Tsuge Y, Yano H, Iwama T, Hayashi S, Hoshi H, Yamada J, Kanematsu M, Aoyama H (2012) Impact of [11C] methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning. Int J Radiat Oncol Biol Phys 82(1):83–89

    Article  Google Scholar 

  14. Miwa K, Shinoda J, Yano H, Okumura A, Iwama T, Nakashima T, Sakai N (2004) 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 75(10):1457–1462

    Article  CAS  Google Scholar 

  15. Nishikawa M, Inoue A, Ohnishi T, Kohno S, Ohue S, Matsumoto S, Suehiro S, Yamashita D, Ozaki S, Watanabe H, Yano H, Takahashi H, Kitazawa R, Tanaka J, Kunieda T (2018) Significance of glioma stem-like cells in the tumor periphery that express high levels of CD44 in tumor invasion, early progression, and poor prognosis in glioblastoma. Stem Cells Int 23:5387041

    Google Scholar 

  16. Oh J, Sahgal A, Sanghera P, Tsao MN, Davey P, Lam K, Symons S, Aviv R, Perry JR (2011) Glioblastoma: patterns of recurrence and efficacy of salvage treatments. Can J Neurol Sci 38(4):621–625

    Article  Google Scholar 

  17. Ohnishi T (2014) Recent progress in surgery of malignant gliomas in and near eloquent cortical areas. J-Stage Prog Neuro Oncol 21(3):1–13

    Google Scholar 

  18. Ohue S, Kohno S, Inoue A, Yamashita D, Harada H, Kumon Y, Kikuchi K, Miki H, Ohnishi T (2012) Accuracy of diffusion tensor magnetic resonance imaging-based tractography for surgery of gliomas near the pyramidal tract: a significant correlation between subcortical electrical stimulation and postoperative tractography. Neurosurgery 70(2):283–293

    Article  Google Scholar 

  19. Ohue S, Kohno S, Inoue A, Yamashita D, Matsumoto S, Suehiro S, Kumon Y, Kikuchi K, Ohnishi T (2015) Surgical results of tumor resection using tractography-integrated navigation-guided fence-post catheter techniques and motor-evoked potentials for preservation of motor function in patients with glioblastomas near the pyramidal tracts. Neurosurg Rev 38(2):293–306

    Article  Google Scholar 

  20. Palanichamy K, Chakravarti A (2017) Diagnostic and prognostic significance of methionine uptake and methionine positron emission tomography imaging in gliomas. Front Oncol 1(7):257

    Article  Google Scholar 

  21. Pirotte BJ, Levivier M, Goldman S, Massager N, Wikler D, Dewitte O, Bruneau M, Rorive S, David P, Brotchi J (2009) Positron emission tomography-guided volumetric resection of supratentorial high-grade gliomas: a survival analysis in 66 consecutive patients. Neurosurgery 64(3):471–481

    Article  Google Scholar 

  22. Roux A, Peeters S, Zanello M, Bou Nassif R, Abi Lahoud G, Dezamis E, Parraga E, Lechapt-Zalcmann E, Dhermain F, Dumont S, Louvel G, Chretien F, Sauvageon X, Devaux B, Oppenheim C, Pallud J (2017) Extent of resection and Carmustine wafer implantation safely improve survival in patients with a newly diagnosed glioblastoma: a single center experience of the current practice. J Neuro-Oncol 135(1):83–92

    Article  Google Scholar 

  23. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828

    CAS  PubMed  Google Scholar 

  24. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996

    Article  CAS  Google Scholar 

  25. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group (2009) 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. Lancet Oncol 10(5):459–466

    Article  CAS  Google Scholar 

  26. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90(12):5002–5012

    Article  CAS  Google Scholar 

  27. Yoo MY, Paeng JC, Cheon GJ, Lee DS, Chung JK, Kim EE, Kang KW (2015) Prognostic value of metabolic tumor volume on (11)C-methionine PET in predicting progression-free survival in high-grade glioma. Nucl Med Mol Imaging 49(4):291–297

    Article  CAS  Google Scholar 

  28. Zhao J, Chen Z, Cai L, Yin S, Yang W, Wang Z (2019) Quantitative volumetric analysis of primary glioblastoma multiforme on MRI and 11C-methionine PET: initial study on five patients. Neurol Neurochir Pol 53(3):199–204

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to express their gratitude to Taichi Furumochi and Yasuhiro Shiraishi of the Department of Neurology, Ehime University Hospital, Japan; and Satsuki Myoga of the Department of Pathology, Ehime University Hospital, Japan, for their help in obtaining the pathologic and radiologic findings.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan

    Akihiro Inoue, Shohei Kohno, Masahiro Nishikawa, Satoshi Suehiro, Shirabe Matsumoto, Saya Ozaki, Seiji Shigekawa, Hideaki Watanabe & Takeharu Kunieda

  2. Department of Neurosurgery, Washoukai Sadamoto Hospital, 1-6-1 Takehara, Matsuyama, Ehime, 790-0052, Japan

    Takanori Ohnishi

  3. Department of Neurosurgery, Ehime Prefectural Central Hospital, 83 Kasuga-machi, Matsuyama, Ehime, 790-0024, Japan

    Shiro Ohue

  4. Division of Diagnostic Pathology, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan

    Mana Fukushima & Riko Kitazawa

  5. Department of Analytical Pathology, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan

    Mie Kurata

Authors
  1. Akihiro Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takanori Ohnishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shohei Kohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shiro Ohue
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masahiro Nishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Satoshi Suehiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shirabe Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Saya Ozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mana Fukushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mie Kurata
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Riko Kitazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Seiji Shigekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hideaki Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Takeharu Kunieda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akihiro Inoue.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants

This study was approved by the Ethics Committee for Clinical Research of Ehime University Hospital (no. 1703011) prior to initiation and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

Representative images of volumetric analysis of GBM. Volumetric analysis of the relationship among the Gd-enhanced area, Met-uptake area, and the area of high intensity on T2WI. The Met-uptake area that was superimposed on the Gd-enhanced image was divided into five subareas according to Met-uptake index, at TNRs of 1.2, 1.4, 1.6, 1.8, and ≧2.0, which are drawn as iso-contour lines as the borderlines of each subarea. (PNG 1027 kb).

High Resolution Image (TIF 240 kb).

ESM 2

Bar graph showing volumetric ratios of Met-uptake area in the 12 patients. In all patients, the Met-uptake area at TNR ≤1.4 was larger than the Gd-enhanced area. (PNG 307 kb).

High Resolution Image (TIF 106 kb).

ESM 3

Immunohistochemical and mRNA expression of glioma stem cell markers, CD133 and nestin in GBMs. Immunohistochemical expression in C-type of GBMs (a). Bar graph showing expression of CD133 in each type of GBMs (b). mRNA expression of CD133 in the tumor core and periphery was determined with qRT-PCR. The values are the relative expression of mRNA of CD133 normalized to the glyceraldehyde 3-phosphate dehydrogenase (GAPDH). In the high-invasiveness type (A- and C-type), the expression of CD133 is higher at the periphery of the tumor than at its core. However, in the low-invasiveness type (B-type), the level of CD133 is lower at the periphery of the tumor than at the core. (PNG 2587 kb).

High Resolution Image (TIF 524 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inoue, A., Ohnishi, T., Kohno, S. et al. Met-PET uptake index for total tumor resection: identification of 11C-methionine uptake index as a goal for total tumor resection including infiltrating tumor cells in glioblastoma. Neurosurg Rev 44, 587–597 (2021). https://doi.org/10.1007/s10143-020-01258-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-020-01258-7

Keywords

Search

Navigation