Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-07-2016 | Original Article

¹⁸F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors

Authors: Takuya Toyonaga, Kenji Hirata, Shigeru Yamaguchi, Kanako C. Hatanaka, Sayaka Yuzawa, Osamu Manabe, Kentaro Kobayashi, Shiro Watanabe, Tohru Shiga, Shunsuke Terasaka, Hiroyuki Kobayashi, Yuji Kuge, Nagara Tamaki

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2016

Abstract

Purpose

Tumor necrosis is one of the indicators of tumor aggressiveness. ¹⁸F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake.

Methods

This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR).

Results

In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively.

Conclusions

FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.

Moradi A, Semnani V, Djam H, Tajodini A, Zali AR, Ghaemi K, et al. Pathodiagnostic parameters for meningioma grading. J Clin Neurosci: Off J Neurosurg Soc Aust. 2008;15(12):1370–5. doi:10.1016/j.jocn.2007.12.005.CrossRef

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109. doi:10.1007/s00401-007-0243-4.CrossRefPubMedPubMedCentral

Miller CR, Dunham CP, Scheithauer BW, Perry A. Significance of necrosis in grading of oligodendroglial neoplasms: a clinicopathologic and genetic study of newly diagnosed high-grade gliomas. J Clin Oncol: Off J Am Soc Clin Oncol. 2006;24(34):5419–26. doi:10.1200/JCO.2006.08.1497.CrossRef

Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190–8. doi:10.3171/jns.2001.95.2.0190.CrossRefPubMed

Urtasun R, Band P, Chapman JD, Feldstein ML, Mielke B, Fryer C. Radiation and high-dose metronidazole in supratentorial glioblastomas. N Engl J Med. 1976;294(25):1364–7. doi:10.1056/NEJM197606172942503.CrossRefPubMed

Dische S. Chemical sensitizers for hypoxic cells: a decade of experience in clinical radiotherapy. Radiother Oncol: J Eur Soc Ther Radiol Oncol. 1985;3(2):97–115.CrossRef

Van Os-Corby DJ, Koch CJ, Chapman JD. Is misonidazole binding to mouse tissues a measure of cellular pO2? Biochem Pharmacol. 1987;36(20):3487–94.CrossRefPubMed

Rasey JS, Nelson NJ, Chin L, Evans ML, Grunbaum Z. Characteristics of the binding of labeled fluoromisonidazole in cells in vitro. Radiat Res. 1990;122(3):301–8.CrossRefPubMed

Kavanagh MC, Sun A, Hu Q, Hill RP. Comparing techniques of measuring tumor hypoxia in different murine tumors: Eppendorf pO2 Histograph, [3H]misonidazole binding and paired survival assay. Radiat Res. 1996;145(4):491–500.CrossRefPubMed

10.

Piert M, Machulla H, Becker G, Stahlschmidt A, Patt M, Aldinger P, et al. Introducing fluorine-18 fluoromisonidazole positron emission tomography for the localisation and quantification of pig liver hypoxia. Eur J Nucl Med. 1999;26(2):95–109.CrossRefPubMed

11.

Piert M, Machulla HJ, Becker G, Aldinger P, Winter E, Bares R. Dependency of the [18F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver. Nucl Med Biol. 2000;27(8):693–700.CrossRefPubMed

12.

Bentzen L, Keiding S, Horsman MR, Gronroos T, Hansen SB, Overgaard J. Assessment of hypoxia in experimental mice tumours by [18F]fluoromisonidazole PET and pO2 electrode measurements. Influence of tumour volume and carbogen breathing. Acta Oncol. 2002;41(3):304–12.CrossRefPubMed

13.

Hirata K, Terasaka S, Shiga T, Hattori N, Magota K, Kobayashi H, et al. (1)(8)F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas. Eur J Nucl Med Mol Imaging. 2012;39(5):760–70. doi:10.1007/s00259-011-2037-0.CrossRefPubMed

14.

Grunbaum Z, Freauff SJ, Krohn KA, Wilbur DS, Magee S, Rasey JS. Synthesis and characterization of congeners of misonidazole for imaging hypoxia. J Nucl Med: Off Publ Soc Nucl Med. 1987;28(1):68–75.

15.

Thorwarth D, Eschmann SM, Paulsen F, Alber M. A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia. Phys Med Biol. 2005;50(10):2209–24. doi:10.1088/0031-9155/50/10/002.CrossRefPubMed

16.

Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med: Off Publ Soc Nucl Med. 2009;50 Suppl 1:122S–50. doi:10.2967/jnumed.108.057307.CrossRef

17.

Kobayashi K, Hirata K, Yamaguchi S, Manabe O, Terasaka S, Kobayashi H, et al. Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients. Eur J Nucl Med Mol Imaging. 2015;42(7):1071–80. doi:10.1007/s00259-015-3046-1.CrossRefPubMed

18.

Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinforma. 2011;12:77. doi:10.1186/1471-2105-12-77.CrossRef

19.

Lee ST, Scott AM. Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole. Semin Nucl Med. 2007;37(6):451–61. doi:10.1053/j.semnuclmed.2007.07.001.CrossRefPubMed

20.

Bell C, Dowson N, Fay M, Thomas P, Puttick S, Gal Y, et al. Hypoxia imaging in gliomas with 18F-fluoromisonidazole PET: toward clinical translation. Semin Nucl Med. 2015;45(2):136–50. doi:10.1053/j.semnuclmed.2014.10.001.CrossRefPubMed

21.

Jenkins WT, Evans SM, Koch CJ. Hypoxia and necrosis in rat 9L glioma and Morris 7777 hepatoma tumors: comparative measurements using EF5 binding and the Eppendorf needle electrode. Int J Radiat Oncol Biol Phys. 2000;46(4):1005–17.CrossRefPubMed

22.

Yamaguchi S, Terasaka S, Kobayashi H, Asaoka K, Motegi H, Nishihara H, et al. Prognostic factors for survival in patients with high-grade meningioma and recurrence-risk stratification for application of radiotherapy. PLoS One. 2014;9(5), e97108. doi:10.1371/journal.pone.0097108.CrossRefPubMedPubMedCentral

23.

Szeto MD, Chakraborty G, Hadley J, Rockne R, Muzi M, Alvord Jr EC, et al. Quantitative metrics of net proliferation and invasion link biological aggressiveness assessed by MRI with hypoxia assessed by FMISO-PET in newly diagnosed glioblastomas. Cancer Res. 2009;69(10):4502–9. doi:10.1158/0008-5472.CAN-08-3884.CrossRefPubMedPubMedCentral

24.

Spence AM, Muzi M, Swanson KR, O’Sullivan F, Rockhill JK, Rajendran JG, et al. Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res: Off J Am Assoc Cancer Res. 2008;14(9):2623–30. doi:10.1158/1078-0432.CCR-07-4995.CrossRef

25.

Swanson KR, Chakraborty G, Wang CH, Rockne R, Harpold HL, Muzi M, et al. Complementary but distinct roles for MRI and 18F-fluoromisonidazole PET in the assessment of human glioblastomas. J Nucl Med: Off Publ Soc Nucl Med. 2009;50(1):36–44. doi:10.2967/jnumed.108.055467.CrossRef

26.

Kawai N, Lin W, Cao WD, Ogawa D, Miyake K, Haba R, et al. Correlation between 18F-fluoromisonidazole PET and expression of HIF-1alpha and VEGF in newly diagnosed and recurrent malignant gliomas. Eur J Nucl Med Mol Imaging. 2014;41(10):1870–8. doi:10.1007/s00259-014-2776-9.CrossRefPubMed

27.

Okamoto S, Shiga T, Yasuda K, Ito YM, Magota K, Kasai K, et al. High reproducibility of tumor hypoxia evaluated by 18F-fluoromisonidazole PET for head and neck cancer. J Nucl Med: Off Publ Soc Nucl Med. 2013;54(2):201–7. doi:10.2967/jnumed.112.109330.CrossRef

Title: 18F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors
Authors: Takuya Toyonaga
Kenji Hirata
Shigeru Yamaguchi
Kanako C. Hatanaka
Sayaka Yuzawa
Osamu Manabe
Kentaro Kobayashi
Shiro Watanabe
Tohru Shiga
Shunsuke Terasaka
Hiroyuki Kobayashi
Yuji Kuge
Nagara Tamaki
Publication date: 01-07-2016
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-016-3320-x

At a glance: The STEP trials

Springer Medicine

¹⁸F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 8/2016

Recurrent prosthetic mitral valve infective endocarditis and perivalvular abscess: first description by PET/CT angiography

Development of a nomogram combining clinical staging with 18F-FDG PET/CT image features in non-small-cell lung cancer stage I–III

Uncontrolled risk factors and worsening perfusion pattern on SPECT myocardial perfusion imaging in medically treated patients with stable chronic ischaemic heart disease

Mirko D’Onofrio, Paola Capelli and Paolo Pederzoli (Eds) Imaging and Pathology of Pancreatic Neoplasms. A Pictorial Atlas

The 2015 Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma: the “evidence-based” refusal to endorse them by EANM due to the “not evidence-based” marginalization of the role of Nuclear Medicine

Intratumoral heterogeneity of 18F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma