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A Review of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography

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Hypoxia

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2755))

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Abstract

Tumor hypoxia is an essential factor related to malignancy, prognosis, and resistance to treatment. Positron emission tomography (PET) is a modality that visualizes the distribution of radiopharmaceuticals administered into the body. PET imaging with [18F]fluoromisonidazole ([18F]FMISO) identifies hypoxic tissues. Unlike [18F]fluorodeoxyglucose ([18F]FDG)-PET, fasting is not necessary for [18F]FMISO-PET, but the waiting time from injection to image acquisition needs to be relatively long (e.g., 2–4 h). [18F]FMISO-PET images can be displayed on an ordinary commercial viewer on a personal computer (PC). While visual assessment is fundamental, various quantitative indices such as tumor-to-muscle ratio have also been proposed. Several novel hypoxia tracers have been invented to compensate for the limitations of [18F]FMISO.

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References

  1. Hirata K, Yamaguchi S, Shiga T, Kuge Y, Tamaki N (2019) The roles of hypoxia imaging using (18)F-fluoromisonidazole positron emission tomography in glioma treatment. J Clin Med 8:1088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kobayashi H, Hirata K, Yamaguchi S, Terasaka S, Shiga T, Houkin K (2013) Usefulness of FMISO-PET for glioma analysis. Neurol Med Chir (Tokyo) 53:773–778

    Article  PubMed  Google Scholar 

  3. Tamaki N, Hirata K (2016) Tumor hypoxia: a new PET imaging biomarker in clinical oncology. Int J Clin Oncol 21:619–625

    Article  CAS  PubMed  Google Scholar 

  4. Toyonaga T, Hirata K, Shiga T, Nagara T (2017) Players of ‘hypoxia orchestra’ – what is the role of FMISO? Eur J Nucl Med Mol Imaging 44:1679–1681

    Article  PubMed  Google Scholar 

  5. Reeves KM, Song PN, Angermeier A, Della Manna D, Li Y, Wang J et al (2022) (18)F-FMISO PET imaging identifies hypoxia and immunosuppressive tumor microenvironments and guides targeted evofosfamide therapy in tumors refractory to PD-1 and CTLA-4 inhibition. Clin Cancer Res 28:327–337

    Article  CAS  PubMed  Google Scholar 

  6. Thureau S, Dubray B, Modzelewski R, Bohn P, Hapdey S, Vincent S et al (2018) FDG and FMISO PET-guided dose escalation with intensity-modulated radiotherapy in lung cancer. Radiat Oncol 13:208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hirata K, Manabe O, Magota K, Furuya S, Shiga T, Kudo K (2021) A preliminary study to use SUVmax of FDG PET-CT as an identifier of lesion for artificial intelligence. Front Med 8:647562

    Article  Google Scholar 

  8. Chapman JD, Franko AJ, Sharplin J (1981) A marker for hypoxic cells in tumours with potential clinical applicability. Br J Cancer 43:546–550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jerabek PA, Patrick TB, Kilbourn MR, Dischino DD, Welch MJ (1986) Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: potential in vivo markers of hypoxic tissue. Int J Rad Appl Instrum A Appl Radiat Isot 37:599–605

    Article  CAS  Google Scholar 

  10. Quartuccio N, Asselin MC (2018) The validation path of hypoxia PET imaging: focus on brain tumours. Curr Med Chem 25:3074–3095

    Article  CAS  PubMed  Google Scholar 

  11. Gouel P, Decazes P, Vera P, Gardin I, Thureau S, Bohn P (2023) Advances in PET and MRI imaging of tumor hypoxia. Front Med 10:1055062

    Article  Google Scholar 

  12. Dolezel M, Slavik M, Blazek T, Kazda T, Koranda P, Veverkova L et al (2022) FMISO-based adaptive radiotherapy in head and neck cancer. J Pers Med 12:1245

    Article  PubMed  PubMed Central  Google Scholar 

  13. Marcus C, Subramaniam RM (2021) Role of non-FDG-PET/CT in head and neck cancer. Semin Nucl Med 51:68–78

    Article  PubMed  Google Scholar 

  14. Yamane T, Aikawa M, Yasuda M, Fukushima K, Seto A, Okamoto K et al (2019) [(18)F]FMISO PET/CT as a preoperative prognostic factor in patients with pancreatic cancer. EJNMMI Res 9:39

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kniess T, Zessin J, Mäding P, Kuchar M, Kiss O, Kopka K (2023) Synthesis of [(18)F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist's perspective. EJNMMI Radiopharm Chem 8:5

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hirata K, Terasaka S, Shiga T, Hattori N, Magota K, Kobayashi H et al (2012) 18F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas. Eur J Nucl Med Mol Imaging 39:760–770

    Article  CAS  PubMed  Google Scholar 

  17. Gouel P, Callonnec F, Obongo-Anga FR, Bohn P, Lévêque E, Gensanne D et al (2023) Quantitative MRI to characterize hypoxic tumors in comparison to FMISO PET/CT for radiotherapy in oropharynx cancers. Cancers 15:1918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Inada M, Nishimura Y, Hanaoka K, Nakamatsu K, Doi H, Uehara T et al (2023) Visualization of tumor hypoxia and re-oxygenation after stereotactic body radiation therapy in early peripheral lung cancer: a prospective study. Radiother Oncol 180:109491

    Article  PubMed  Google Scholar 

  19. Thorwarth D, Eschmann SM, Paulsen F, Alber M (2005) A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia. Phys Med Biol 50:2209–2224

    Article  PubMed  Google Scholar 

  20. Vera P, Bohn P, Edet-Sanson A, Salles A, Hapdey S, Gardin I et al (2011) Simultaneous positron emission tomography (PET) assessment of metabolism with 18F-fluoro-2-deoxy-d-glucose (FDG), proliferation with 18F-fluoro-thymidine (FLT), and hypoxia with 18fluoro-misonidazole (F-miso) before and during radiotherapy in patients with non-small-cell lung cancer (NSCLC): a pilot study. Radiother Oncol 98:109–116

    Article  CAS  PubMed  Google Scholar 

  21. Cher LM, Murone C, Lawrentschuk N, Ramdave S, Papenfuss A, Hannah A et al (2006) Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies. J Nucl Med 47:410–418

    CAS  PubMed  Google Scholar 

  22. Kobayashi K, Manabe O, Hirata K, Yamaguchi S, Kobayashi H, Terasaka S et al (2020) Influence of the scan time point when assessing hypoxia in (18)F-fluoromisonidazole PET: 2 vs. 4 h. Eur J Nucl Med Mol Imaging 47:1833–1842

    Article  CAS  PubMed  Google Scholar 

  23. Bourigault P, Skwarski M, Macpherson RE, Higgins GS, McGowan DR (2022) Timing of hypoxia PET/CT imaging after 18F-fluoromisonidazole injection in non-small cell lung cancer patients. Sci Rep 12:21746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Thureau S, Chaumet-Riffaud P, Modzelewski R, Fernandez P, Tessonnier L, Vervueren L et al (2013) Interobserver agreement of qualitative analysis and tumor delineation of 18F-fluoromisonidazole and 3′-deoxy-3′-18F-fluorothymidine PET images in lung cancer. J Nucl Med 54:1543–1550

    Article  CAS  PubMed  Google Scholar 

  25. Choen S, Kent MS, Chaudhari AJ, Cherry SR, Krtolica A, Zwingenberger AL (2023) Kinetic evaluation of the hypoxia radiotracers [(18)F]FMISO and [(18)F]FAZA in dogs with spontaneous tumors using dynamic PET/CT imaging. Nucl Med Mol Imaging 57:16–25

    Article  CAS  PubMed  Google Scholar 

  26. Akamatsu G, Ishikawa K, Mitsumoto K, Taniguchi T, Ohya N, Baba S et al (2012) Improvement in PET/CT image quality with a combination of point-spread function and time-of-flight in relation to reconstruction parameters. J Nucl Med 53:1716–1722

    Article  PubMed  Google Scholar 

  27. Kadrmas DJ, Casey ME, Conti M, Jakoby BW, Lois C, Townsend DW (2009) Impact of time-of-flight on PET tumor detection. J Nucl Med 50:1315–1323

    Article  PubMed  Google Scholar 

  28. Tong S, Alessio AM, Kinahan PE (2009) Evaluation of noise properties in PSF-based PET image reconstruction. IEEE Nucl Sci Symp Conf Rec 2009:3042–3047

    Google Scholar 

  29. Miwa K, Yoshii T, Wagatsuma K, Nezu S, Kamitaka Y, Yamao T et al (2023) Impact of γ factor in the penalty function of Bayesian penalized likelihood reconstruction (Q.Clear) to achieve high-resolution PET images. EJNMMI. Physics 10:4

    Google Scholar 

  30. Kim K, Wu D, Gong K, Dutta J, Kim JH, Son YD et al (2018) Penalized PET reconstruction using deep learning prior and local linear fitting. IEEE Trans Med Imaging 37:1478–1487

    Article  PubMed  PubMed Central  Google Scholar 

  31. Gong K, Catana C, Qi J, Li Q (2019) PET image reconstruction using deep image prior. IEEE Trans Med Imaging 38:1655–1665

    Article  PubMed  Google Scholar 

  32. Schaefferkoetter J, Shah V, Hayden C, Prior JO, Zuehlsdorff S (2023) Deep learning for improving PET/CT attenuation correction by elastic registration of anatomical data. Eur J Nucl Med Mol Imaging 50:2292–2304

    Article  PubMed  Google Scholar 

  33. Shi L, Zhang J, Toyonaga T, Shao D, Onofrey JA, Lu Y (2023) Deep learning-based attenuation map generation with simultaneously reconstructed PET activity and attenuation and low-dose application. Phys Med Biol 68:035014. https://doi.org/10.1088/1361-6560/acaf49

    Article  Google Scholar 

  34. Singh MK, Mohan P, Mahajan H, Kaushik C (2023) Technical and clinical assessment of latest technology SiPM integrated digital PETCT scanner. Radiography (London, England: 1995) 29:705–711

    CAS  PubMed  Google Scholar 

  35. Hirata K, Kobayashi K, Wong KP, Manabe O, Surmak A, Tamaki N et al (2014) A semi-automated technique determining the liver standardized uptake value reference for tumor delineation in FDG PET-CT. PLoS One 9:e105682

    Article  PubMed  PubMed Central  Google Scholar 

  36. Yamaguchi S, Hirata K, Toyonaga T, Kobayashi K, Ishi Y, Motegi H et al (2016) Change in 18F-fluoromisonidazole PET is an early predictor of the prognosis in the patients with recurrent high-grade glioma receiving bevacizumab treatment. PLoS One 11:e0167917

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kroenke M, Hirata K, Gafita A, Watanabe S, Okamoto S, Magota K et al (2019) Voxel based comparison and texture analysis of 18F-FDG and 18F-FMISO PET of patients with head-and-neck cancer. PLoS One 14:e0213111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Toyonaga T, Yamaguchi S, Hirata K, Kobayashi K, Manabe O, Watanabe S et al (2017) Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor. Eur J Nucl Med Mol Imaging 44:611–619

    Article  CAS  PubMed  Google Scholar 

  39. Drake LR, Hillmer AT, Cai Z (2020) Approaches to PET imaging of glioblastoma. Molecules 25:568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Toriihara A, Ohtake M, Tateishi K, Hino-Shishikura A, Yoneyama T, Kitazume Y et al (2018) Prognostic implications of (62)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) PET/CT in patients with glioma. Ann Nucl Med 32:264–271

    Article  CAS  PubMed  Google Scholar 

  41. Hu M, Zhu Y, Mu D, Fan B, Zhao S, Yang G et al (2020) Correlation of hypoxia as measured by fluorine-18 fluoroerythronitroimidazole ((18)F-FETNIM) PET/CT and overall survival in glioma patients. Eur J Nucl Med Mol Imaging 47:1427–1434

    Article  CAS  PubMed  Google Scholar 

  42. Han K, Fyles A, Shek T, Croke J, Dhani N, D'Souza D et al (2022) A phase II randomized trial of chemoradiation with or without metformin in locally advanced cervical cancer. Clin Cancer Res 28:5263–5271

    Article  CAS  PubMed  Google Scholar 

  43. Narva SI, Seppänen MP, Raiko JRH, Forsback SJ, Orte KJ, Virtanen JM et al (2021) Imaging of tumor hypoxia with 18F-EF5 PET/MRI in cervical cancer. Clin Nucl Med 46:952–957

    Article  PubMed  Google Scholar 

  44. Köthe A, Bizzocchi N, Safai S, Lomax AJ, Weber DC, Fattori G (2021) Investigating the potential of proton therapy for hypoxia-targeted dose escalation in non-small cell lung cancer. Radiat Oncol 16:199

    Article  PubMed  PubMed Central  Google Scholar 

  45. Watanabe S, Shiga T, Hirata K, Magota K, Okamoto S, Toyonaga T et al (2019) Biodistribution and radiation dosimetry of the novel hypoxia PET probe [(18)F]DiFA and comparison with [(18)F]FMISO. EJNMMI Res 9:60

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was partly supported by JSPS KAKENHI Grant Numbers JP22H03285 and JP20K16781.

Author information

Authors and Affiliations

  1. Department of Diagnostic Imaging, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Kenji Hirata, Shiro Watanabe & Kohsuke Kudo

  2. Department of Nuclear Medicine, Hokkaido University Hospital, Sapporo, Japan

    Kenji Hirata, Shiro Watanabe & Kohsuke Kudo

  3. Global Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Kenji Hirata & Shiro Watanabe

  4. Oral Diagnosis and Medicine, Department of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

    Yoshimasa Kitagawa

  5. Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan

    Kohsuke Kudo

Authors
  1. Kenji Hirata
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  2. Shiro Watanabe
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  3. Yoshimasa Kitagawa
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  4. Kohsuke Kudo
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Corresponding author

Correspondence to Kenji Hirata .

Editor information

Editors and Affiliations

  1. Department of Oncology Johns Hopkins, University School of Medicine, Baltimore, MD, USA

    Daniele M. Gilkes

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© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Hirata, K., Watanabe, S., Kitagawa, Y., Kudo, K. (2024). A Review of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography. In: Gilkes, D.M. (eds) Hypoxia. Methods in Molecular Biology, vol 2755. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3633-6_9

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  • DOI: https://doi.org/10.1007/978-1-0716-3633-6_9

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3632-9

  • Online ISBN: 978-1-0716-3633-6

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