Skip to main content
SpringerLink
Log in

Hypoxia Imaging for Radiation Therapy Planning

  • Chapter
  • First Online:
Therapeutic Nuclear Medicine

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

  • 2639 Accesses

Abstract

Hypoxia is one of the key features conferring resistance to oncologic treatment. Modern radiotherapy aims at overcoming hypoxia-induced resistance by escalating or redistributing dose or by modulating the sensitivity of poorly oxygenated but viable tumour cells. To accomplish this, it is necessary to detect hypoxia both spatially and temporally and to recognise limitations in sensitivity to differentiate oxic and hypoxic tumour subvolumes. Currently, PET/CT-based imaging using radiolabelled nitroimidazole or thiosemicarbazone compounds is the preferred technique for biological dose planning targeting hypoxia. Hypoxic tumour cells identified on PET/CT may be treated by giving a graded higher dose in a limited number of hypoxic compartments or by individually prescribing a dose to each volume unit based on 3D mapping of tumour oxygenation status. The latter technique is commonly called dose painting by numbers (DPN) to illustrate the heterogeneous dose received by the hypoxic target. Dose planning requires sophisticated computer algorithms where intensity-modulated radiotherapy (IMRT) is used to deliver irradiation. It is not yet known which strategy for planning and delivering hypoxia-targeted radiotherapy is the most appropriate in the clinical setting and what role chemical and biological modifiers of oxygenation will play given the lack of outcome data. Furthermore, adaptive strategies accounting for the effect of reoxygenation and cyclic hypoxia should be studied as well. This chapter outlines biological, methodological and technical issues associated with hypoxia-directed radiation therapy planning with emphasis on their potential application in clinical practice.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ATSM:

Thiosemicarbazone ligands

BTV:

Biological target volume

DCEMRI:

Dynamic contrast-enhanced magnetic resonance imaging

DPN:

Dose painting by numbers

EF5:

Pentafluoropropylacetamide

FAZA:

Fluoroazomycin-arabinofuranosine

FDG:

Fluorodeoxyglucose

FMISO:

Fluoromisonidazole

HF:

Hypoxic fraction

HIF:

Hypoxia-inducible factor

IMRT:

Intensity-modulated radiotherapy

IGRT:

Image guided radiotherapy

NTCP:

Normal tissue complication probability

OER:

Oxygen enhancement ratio

RT:

Radiotherapy

SCC:

Squamous cell carcinoma

SNR:

Signal-to-noise ratio

TCP:

Tumour control probability

VOI:

Volume of interest

References

  • Bentzen SM (2005) Theragnostic imaging for radiation oncology: dose-painting by numbers. Lancet Oncol 6:112–117

    Article  PubMed  Google Scholar 

  • Busk M, Horsman MR, Overgaard J (2008) Resolution in PET hypoxia imaging: voxel size matters. Acta Oncol 47:1201–1210

    Article  PubMed  Google Scholar 

  • Carlson DJ, Stewart RD, Semenenko VA (2006) Effects of oxygen on intrinsic radiation sensitivity: a test of the relationship between aerobic and hypoxic linear-quadratic (LQ) model parameters. Med Phys 33:3105–3115

    Article  CAS  PubMed  Google Scholar 

  • Chao KS, Bosch WR, Mutic S et al (2001) A novel approach to overcome hypoxic tumour resistance: Cu-ATSM-guided intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys 49:1171–1182

    Article  CAS  PubMed  Google Scholar 

  • Christian N, Lee JA, Bol A et al (2009) The limitation of PET imaging for biological adaptive-IMRT assessed in animal models. Radiother Oncol 91:101–106

    Article  PubMed  Google Scholar 

  • Dewhirst MW (2009) Relationships between cycling hypoxia, HIF-1, angiogenesis and oxidative stress. Radiat Res 172:653–665

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dewhirst MW, Cao Y, Moeller B (2008) Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 8:425–438

    Article  CAS  Google Scholar 

  • El-Naqa I, Yang D, Apte A et al (2007) Concurrent multimodality image segmentation by active contours for radiotherapy treatment planning. Med Phys 34:4738–4749

    Article  PubMed  Google Scholar 

  • Eschmann S, Paulsen F, Reimold M et al (2005) Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 46:253–260

    PubMed  Google Scholar 

  • Geets X, Lee JA, Bol A et al (2007) A gradient-based method for segmenting FDG-PET images: methodology and validation. Eur J Nucl Med Mol Imaging 34:1427–1438

    Article  PubMed  Google Scholar 

  • Grosu AL, Souvatzoglou M, Röper B et al (2007) Hypoxia imaging with FAZA-PET and theoretical considerations with regard to dose painting for individualization of radiotherapy in patients with head and neck cancer. Int J Radiat Oncol Biol Phys 69:541–551

    Article  CAS  PubMed  Google Scholar 

  • Hatt M, le Rest C, Turzo A et al (2009) A fuzzy locally adaptive Bayesian segmentation approach for volume determination in PET. IEEE Trans Med Im 28:881–893

    Article  Google Scholar 

  • Horsman MR, Wouters BG, Joiner MC, Overgaard J (2009) The oxygen effect and fractionated radiotherapy. In: Joiner M, van der Kogel A (eds) Basic clinical radiobiology. Edward Arnold, London, pp 207–216

    Chapter  Google Scholar 

  • Horsman MR, van der Kogel A (2009) Therapeutic approaches to tumour hypoxia. In: Joiner M, van der Kogel A (eds) Basic clinical radiobiology. Edward Arnold, London, pp 233–245

    Chapter  Google Scholar 

  • Koh WJ, Bergman KS, Rasey JS et al (1995) Evaluation of oxygenation status during fractionated radiotherapy in human non-small cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. Int J Radiat Oncol Biol Phys 33:391–398

    Article  CAS  PubMed  Google Scholar 

  • Komar G, Seppänen M, Eskola O et al (2008) 18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer. J Nucl Med 49:1944–1951

    Article  PubMed  Google Scholar 

  • Krohn KA, Link JM, Mason RP (2008) Molecular imaging of hypoxia. J Nucl Med 49:129S–148S

    Article  CAS  PubMed  Google Scholar 

  • Lee NY, Mechalakos JG, Nehmeh S et al (2008) Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study. Int J Radiat Oncol Biol Phys 70:2–13

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lin Z, Mechalakos J, Nehmeh S et al (2008) The influence of changes in tumour hypoxia on dose-painting treatment plans based on 18F-FMISO positron emission tomography. Int J Radiat Oncol Biol Phys 70:1219–1228

    Article  PubMed Central  PubMed  Google Scholar 

  • Ling CC, Humm J, Larson S et al (2000) Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys 47:551–560

    Article  CAS  PubMed  Google Scholar 

  • Mackay RI, Hendry JH (1999) The modelled benefits of individualizing radiotherapy patients’ dose using cellular radiosensitivity assays with inherent variability. Radiother Oncol 50:67–75

    Article  CAS  PubMed  Google Scholar 

  • Madani I, Duprez F, Boterberg T et al (2011) Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers for head and neck cancer. Radiother Oncol 101:351–355

    Article  PubMed  Google Scholar 

  • Malinen E, Søvik A, Hristov D et al (2006) Adapting radiotherapy to hypoxic tumours. Phys Med Biol 51:4903–4921

    Article  CAS  PubMed  Google Scholar 

  • Mees G, Dierckx R, Vangestel C et al (2009) Molecular imaging of hypoxia with radiolabelled agents. Eur J Nucl Med Mol Imaging 36:1674–1686

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Minn H, Grönroos TJ, Komar G et al (2008) Imaging of tumour hypoxia to predict treatment sensitivity. Curr Pharm Design 14:2932–2942

    Article  CAS  Google Scholar 

  • Nehmeh SA, Schoder H, Lee NY et al (2008) Reproducibility of the intra-tumoral distribution of 18F-flouromisonidazole (18FMISO) in head and neck cancer. Int J Radiat Oncol Biol Phys 70:235–242

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nordsmark M, Bentzen SM, Rudat V et al (2005) Prognostic value of tumour oxygenation in 397 head and neck tumours after primary radiation therapy. An international multi-center study. Radiother Oncol 77:18–24

    Google Scholar 

  • O’Donoghue JA, Zanzonico P, Pugachev A et al (2005) Assessment of regional tumour hypoxia using 18F-fluoromisonidazole and 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) positron emission tomography: comparative study featuring microPET imaging, Po2 probe measurement, autoradiography, and fluorescent microscopy in the R3327-AT and FaDu rat tumour models. Int J Radiat Oncol Biol Phys 61:1493–1502

    Article  PubMed  Google Scholar 

  • Overgaard J (2011) Hypoxic modification of radiotherapy in squamous cell carcinoma of the head and neck—a systematic review and meta-analysis. Radiother Oncol 100:22–32

    Article  PubMed  Google Scholar 

  • Petit SF, Dekker AL, Seigneuric R et al (2009) Intra-voxel heterogeneity influences the dose prescription for dose-painting with radiotherapy: a modelling study. Phys Med Biol 54:2179–2196

    Article  PubMed  Google Scholar 

  • Popple RA, Ove R, Shen S (2002) Tumour control probability for selective boosting of hypoxic subvolumes, including the effect of reoxygenation. Int J Radiat Oncol Biol Phys 54:921–927

    Article  PubMed  Google Scholar 

  • Rajendran JG, Schwartz DL, O’Sullivan J et al (2006a) Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res 12:5435–5441

    Article  CAS  PubMed  Google Scholar 

  • Rajendran JG, Hendrickson KRG, Spence AM et al (2006b) Hypoxia imaging-directed radiation treatment planning. Eur J Nucl Med Mol Imaging 33:S44–S53

    Article  Google Scholar 

  • Rasey JS, Koh WJ, Evans ML et al (1996) Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 36:417–428

    Article  CAS  PubMed  Google Scholar 

  • Rischin D, Hicks RJ, Fisher R et al (2006) Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumour hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02. J Clin Oncol 24:2098–2104

    Article  PubMed  Google Scholar 

  • Shepherd T, Owenius R (2012) Gaussian process models of dynamic PET for functional volume definition in radiation oncology. IEEE Trans Med Imaging 38:1542–1556

    Google Scholar 

  • South CP, Evans PM, Partridge M (2009) Dose prescription complexity versus tumour control probability in biologically conformal radiotherapy. Med Phys 36:4379–4388

    Article  CAS  PubMed  Google Scholar 

  • Souvatzoglou M, Grosu AL, Röper B et al (2007) Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study. Eur J Nucl Med Mol Imaging 34:1566–1575

    Article  CAS  PubMed  Google Scholar 

  • Søvik A, Malinen E, Skogmo HK et al (2007a) Radiotherapy adapted to spatial and temporal variability in tumour hypoxia. Int J Radiat Oncol Biol Phys 68:1496–1504

    Article  PubMed  Google Scholar 

  • Søvik A, Malinen E, Bruland ØS et al (2007b) Optimization of tumour control probability in hypoxic tumours by radiation dose redistribution: a modelling study. Phys Med Biol 52:499–513

    Article  PubMed  Google Scholar 

  • Søvik A, Malinen E, Olsen DR (2009) Strategies for biologic image-guided dose escalation: a review. Int J Radiat Oncol Biol Phys 73:650–658

    Article  PubMed  Google Scholar 

  • Stephen RM, Gillies RJ (2007) Promise and progress for functional and molecular imaging of response to targeted therapies. Pharm Res 24:1172–1185

    Article  CAS  PubMed  Google Scholar 

  • Stewart FA, Dörr W (2009) Milestones in normal tissue radiation biology over the past 50 years: from clonogenic survival to cytokine networks and back to stem cell recovery. Int J Radiat Biol 85:574–586

    Article  CAS  PubMed  Google Scholar 

  • Stewart RD, Li XA (2007) BGRT: biologically guided radiation therapy—the future is fast approaching! Med Phys 34:3739–3751

    Google Scholar 

  • Thorwarth D, Eschmann S, Paulsen F et al (2007) Hypoxia dose painting by numbers: a planning study. Int J Radiat Oncol Biol Phys 68:291–300

    Article  PubMed  Google Scholar 

  • Thorwarth D, Alber M (2010) Implementation of hypoxia imaging into treatment planning and delivery. Radiother Oncol 97:172–175

    Article  PubMed  Google Scholar 

  • Toma-Daşu I, Daşu A, Brahme A (2009) Dose prescription and optimisation based on tumour hypoxia. Acta Oncol 48:1181–1192

    Article  PubMed  Google Scholar 

  • Tomé WA, Fowler JF (2000) Selective boosting of tumour subvolumes. Int J Radiat Oncol Biol Phys 48:593–599

    Article  PubMed  Google Scholar 

  • Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Met Rev 26:225–239

    Article  CAS  Google Scholar 

  • Zaidi H (2006) Medical image segmentation: Quo Vadis (Editorial). Comput Methods Prog Biomed 84:63–65

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology and Radiotherapy, Turku University Hospital, P.O. Box 52, Turku, Finland

    Heikki Minn

  2. Cancer Center, Kuopio University Hospital, P.O. Box 1777, Kuopio, Finland

    Jan Seppälä

  3. Turku PET Centre, Turku University Hospital, P.O. Box 52, Turku, Finland

    Tony Shepherd

Authors
  1. Heikki Minn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan Seppälä
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tony Shepherd
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heikki Minn .

Editor information

Editors and Affiliations

  1. THERANOSTICS Center for Molecular, Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Bad Berka, Germany

    Richard P. Baum

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Minn, H., Seppälä, J., Shepherd, T. (2012). Hypoxia Imaging for Radiation Therapy Planning. In: Baum, R. (eds) Therapeutic Nuclear Medicine. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2012_690

Download citation

  • DOI: https://doi.org/10.1007/174_2012_690

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-36718-5

  • Online ISBN: 978-3-540-36719-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation