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Nuklearmedizin 2011; 50(01): 22-27
DOI: 10.3413/nukmed-00328-10-07
Original article
Schattauer GmbH

Two or four hour [18F]FMISO-PET in HNSCC

When is the contrast best?Zwei oder vier Stunden [18F]FMISO-PET in Kopf-Hals-KarzinomenWann ist der Bildkontrast am höchsten?
N. Abolmaali
1   OncoRay – Imaging, National Center for Radiation Research in Oncology, TU Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Germany
,
R. Haase
1   OncoRay – Imaging, National Center for Radiation Research in Oncology, TU Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Germany
,
A. Koch
1   OncoRay – Imaging, National Center for Radiation Research in Oncology, TU Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Germany
,
D. Zips
1   OncoRay – Imaging, National Center for Radiation Research in Oncology, TU Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Germany
,
J. Steinbach
1   OncoRay – Imaging, National Center for Radiation Research in Oncology, TU Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Germany
,
M. Baumann
1   OncoRay – Imaging, National Center for Radiation Research in Oncology, TU Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Germany
,
J. Kotzerke
1   OncoRay – Imaging, National Center for Radiation Research in Oncology, TU Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Germany
,
K. Zöphel
1   OncoRay – Imaging, National Center for Radiation Research in Oncology, TU Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Germany
› Author Affiliations
Further Information

Publication History

received: 02 July 2010

accepted in revised form: 17 November 2010

Publication Date:
28 December 2017 (online)

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Summary

[18F]Fluoromisonidazole positron emission tomography (FMISO-PET) is a non invasive imaging technique that can assist detecting intra tumour regions of hypoxia. FMISO-PET evinces comparatively low signal-to-noise-ratio (SNR) and may be acquired dynamically or after different uptake times post injection (p. i.). The aim of this study was to identify, if static images acquired two hours (MISO2) or four hours (MISO4) p. i. reveal higher contrast. Patients, methods: As part of a prospective trial, 23 patients with cancers of the head and neck underwent [18F]fluoro deoxyglucose (FDG) PET before and during curative radiochemotherapy. Additionally, FMISO-PET studies 2 h and 4 h p. i. were done before treatment and after a mean dose of 11 Gy, 23 Gy and 57 Gy during RCT. After coregistration, a dedicated software was used to define the gross tumour volume (GTV) by FDG PET for the primary tumour. This volume was overlaid to the FMISO images and hypoxia within the GTV was determined. The contrast between hypoxia determined by MISO2 and by MISO4 was investigated and analysed with the Wilcoxon-matched-pairs test. Results: Mean SUVmax in tumours of all examinations was 2.2 (stdev: 0.4, min: 1.3, max: 3.4) after 2 h and 2.4 (stdev: 0.7, min: 1.1, max: 4.4) after 4 h. In the neck musculature the mean SUVmax was 1.5 at both time points and the mean SUVmean decreased from 1.2 after 2 h to 1.1 after 4 h, respectively. These effects resulted in significantly rising contrast ratios from MISO2 to MISO4. The differently defined contrasts revealed significantly higher values for examinations 4 h p. i. (p < 0.002). Conclusion: Data acquisition of [18F]FMISO should be done 4 h p. i. to gather the optimal contrast, preferably allowing further analysis, e. g. hypoxic sub volume definition for therapy planning.

Zusammenfassung

Die [18F]Fluormisonidazol-Positronenemissionstomographie (FMISO-PET) ist ein nicht invasives Bildgebungsverfahren, das hypoxische Subvolumina in Tumoren detektieren kann. Die FMISO-PET kann dynamisch oder statisch nach unterschiedlichen Uptakezeiten post injectionem (p.i.) akquiriert werden, hat aber ein vergleichsweise niedriges Signal zu Rausch Verhältnis (SNR). Ziel dieser Studie war es für spätere Analysen zu klären, ob der Bildkontrast in statisch aufgenommenen Untersuchungen nach einer Uptakezeit von zwei Stunden (MISO2) oder vier Stunden (MISO4) p.i. höher ist. Patienten, Methoden: Bei einer Subgruppe von 23 Patienten einer prospektiven Studie zur kurativen Radiochemotherapie (RCT) von Plattenepithelkarzinomen des Hals-Nasen-Rachen-Raumes (HNSCC) wurden vor und während der Therapie [18F]Fluordeoxyglukose (FDG-)PET-Untersuchungen durchgeführt. Zusätzlich wurden bei diesen Patienten FMISO-PET-Aufnahmen zwei und vier Stunden p.i. nach Strahlentherapiedosen von im Mittel 11Gy, 23Gy und 57Gy während der RCT akquiriert. Nach Koregistrierung aller PET- und CT-Datensätze wurde die Rover-Software (ABX, Radeberg) verwendet, um das aus der FDG-PET abgeleitete „gross tumour volume” der Primärtumoren festzulegen. Diese Volumina wurden in die FMISO-Datensätze kopiert um Hypoxie innerhalb des Primärtumors zu definieren. Der Kontrast zwischen hypoxischen Regionen in den Aufnahmen MISO2 und MISO4 wurde untersucht und mit dem Wilcoxon-Rangsummen-Test auf signifikante Unterschiede geprüft. Ergebnisse: Der mittlere SUVmax der Primärtumoren aller Untersuchungen war 2.2 (stdev: 0.4, min: 1.3, max: 3.4) nach 2 h p.i. und 2.4 (stdev: 0.7, min: 1.1, max: 4.4) nach 4 h p.i.. Der mittlere SUVmax in der Nackenmuskulatur war zwei und vier Stunden p.i. 1.5 und der mittlere SUVmean fiel von 1.2 nach 2 h auf 1.1 nach 4 h ab. Diese geringen Veränderungen bedingten aber einen steigenden Kontrast von MISO2 nach MISO4. Für die unterschiedlich definierten Kontraste ergab der Wilcoxon-Rangsummen-Test signifikant höhere Werte in den Untersuchungen vier Stunden p.i. (p < 0.002). Schlussfolgerung: Die Datenakquisition für die [18F]FMISO-PET sollte vorzugsweise vier Stunden p.i. erfolgen, da der Kontrast zwei Stunden p.i. schlechter ist. Diese Datensätze eignen sich deshalb besser für weitere Analysen, z.B.für die verbesserte Definition hypoxischer Tumorsubvolumina zur Strahlentherapieplanung.

Keywords

FMISO PET - head and neck cancer - tumour-tomuscle-ratio - contrast-to-noise-ratio - bio-imaging - radiotherapy treatment planning

Schlüsselwörter

FMISO PET - Kopf/Hals-Tumoren - Tumor-zu-Muskel-Signalverhältnis - Kontrast-zu-Rausch-Verhältnis - Bioimaging - Strahlentherapie-planung
 

  • References

  • 1 Brizel DM, Sibley GS, Prosnitz LR. et al. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 1997; 38: 285-289.
    CrossrefGoogle Scholar
  • 2 Busk M, Horsman MR, Jakobsen S. et al. Can hypoxia- PET map hypoxic cell density heterogeneity accurately in an animal tumor model at a clinically obtainable image contrast?. Radiother Oncol 2009; 92: 429-436.
    CrossrefGoogle Scholar
  • 3 Daisne JF, Duprez T, Weynand B. et al. Tumor volume in pharyngolaryngeal squamous cell carcinoma: comparison at CT, MR imaging, and FDG PET and validation with surgical specimen. Radiology 2004; 233: 93-100.
    CrossrefGoogle Scholar
  • 4 Dirix P, Vandecaveye V, De Keyzer F. et al. Dose painting in radiotherapy for head and neck squamous cell carcinoma: value of repeated functional imaging with 18F-FDG PET, 18F-fluoromisonidazole PET, diffusion-weighted MRI, and dynamic contrast-enhanced MRI. J Nucl Med 2009; 50: 1020-1027.
    CrossrefGoogle Scholar
  • 5 Dubois L, Landuyt W, Cloetens L. et al. [18F]EF3 is not superior to [18F]FMISO for PET-based hypoxia evaluation as measured in a rat rhabdomyosarcoma tumour model. Eur J Nucl Med Mol Imaging 2009; 36: 209-218.
    CrossrefGoogle Scholar
  • 6 Eschmann SM, Paulsen F, Bedeshem C. et al. Hypoxia-imaging with 18F-Misonidazole and PET: changes of kinetics during radiotherapy of head- and-neck cancer. Radiother Oncol 2007; 83: 406-410.
    CrossrefGoogle Scholar
  • 7 Eschmann SM, Paulsen F, Reimold M. et al. Prognostic impact of hypoxia imaging with 18F-misoni- dazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 2005; 46: 253-260.
    Google Scholar
  • 8 Grunbaum Z, Freauff SJ, Krohn KA. et al. Synthesis and characterization of congeners of misonidazole for imaging hypoxia. J Nucl Med 1987; 28: 68-75.
    Google Scholar
  • 9 Hentschel M, Appold S, Schreiber A. et al. Serial FDG-PET on patients with head and neck cancer: implications for radiation therapy. Int J Radiat Biol 2009; 85: 796-804.
    CrossrefPubMedGoogle Scholar
  • 10 Hicks RJ, Rischin D, Fisher R. et al. Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent. Eur J Nucl Med Mol Imaging 2005; 32: 1384-1391.
    CrossrefGoogle Scholar
  • 11 Hockel M, Knoop C, Schlenger K. et al. Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 1993; 26: 45-50.
    CrossrefGoogle Scholar
  • 12 Hofheinz F, Dittrich S, Pötzsch C. et al. Effects of cold sphere walls in PET phantom measurements on the volume reproducing threshold. Phys Med Biol 2010; 55: 1099-1113.
    CrossrefGoogle Scholar
  • 13 Hofheinz F, Poetzsch C, van den Hoff J. Quantitative 3D ROI volume delineation in PET: algorithm and validation. J Nucl Med 2007; 48: 1709.
    Google Scholar
  • 14 Kotzerke J, Oehme L, Lindner O, Hellwig D. Positron emission tomography 2008 in Germany. Nuklearmedizin 2010; 49: 58-64.
    Article in Thieme ConnectGoogle Scholar
  • 15 Lee NY, Mechalakos JG, Nehmeh S. et al. 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 2008; 70: 2-13.
    CrossrefGoogle Scholar
  • 16 Lin Z, Mechalakos J, Nehmeh S. et al. The influence of changes in tumor hypoxia on dose-painting treatment plans based on 18F-FMISO positron emission tomography. Int J Radiat Oncol Biol Phys 2008; 70: 1219-1228.
    CrossrefGoogle Scholar
  • 17 Linecker A, Kermer C, Sulzbacher I. et al. Uptake of 18F-FLT and 18F-FDG in primary head and neck cancer correlates with survival. Nuklearmedizin 2008; 47: 80-85.
    Article in Thieme ConnectGoogle Scholar
  • 18 Nehmeh SA, Lee NY, Schroder H. et al. Reproducibility of intratumor distribution of 18F-fluoro - misonidazole in head and neck cancer. Int J Radiat Oncol Biol Phys 2008; 70: 235-242.
    CrossrefPubMedGoogle Scholar
  • 19 Nunn A, Linder K, Strauss HW. Nitroimidazoles and imaging hypoxia. Eur J Nucl Med 1995; 22: 265-280.
    CrossrefPubMedGoogle Scholar
  • 20 Padhani AR, Krohn KA, Lewis JS, Alber M. Imaging oxygenation of human tumours. Eur Radiol 2007; 17: 861-872.
    CrossrefGoogle Scholar
  • 21 Rajendran JG, Krohn KA. Imaging hypoxia and angiogenesis in tumors. Radiol Clin North Am 2005; 43: 169-187.
    CrossrefGoogle Scholar
  • 22 Rajendran JG, Wilson DC, Conrad EU. et al. [18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas. Eur J Nucl Med Mol Imaging 2003; 30: 695-704.
    CrossrefGoogle Scholar
  • 23 Rasey JS, Koh WJ, Evans ML. et al. Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole. Int J Radiat Oncol Biol Phys 1996; 36: 417-428.
    CrossrefGoogle Scholar
  • 24 Rischin D, Hicks RJ, Fisher R. et al. Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapaza- mine. J Clin Oncol 2006; 24: 2098-2104.
    CrossrefGoogle Scholar
  • 25 Schuetze C, Bergmann R, Mosch B. et al. The impact of pretreatment [18F]FMISO hypoxic volume on local control after single dose irradiation in FaDu HNSCC in nude mice. Radiother Oncol 2009; 90: 55.
    Google Scholar
  • 26 Tang G, Wang M, Tang X. et al. Fully automated one- pot synthesis of [18F]fluoromisonidazole. Nucl Med Biol 2005; 32: 553-558.
    CrossrefGoogle Scholar
  • 27 Thorwarth D, Eschmann S-M, Scheiderbauer J. et al. Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer. BMC Cancer 2005; 5: 152.
    CrossrefGoogle Scholar
  • 28 Troost EG, Laverman P, Philippens ME. et al. Correlation of [18F]FMISO autoradiography and pimon- idazole immunohistochemistry in human head and neck carcinoma xenografts. Eur J Nucl Med Mol Imaging 2008; 35: 1803-1811.
    CrossrefGoogle Scholar
  • 29 Wang W, Lee NY, Georgi JC. et al. Pharmacokinetic analysis of hypoxia 18F-fluoromisonidazole dynamic PET in head and neck cancer. J Nucl Med 2010; 51: 37-45.
    CrossrefGoogle Scholar
  • 30 Wyss MT, Honer M, Schubiger PA, Ametamey SM. NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours. Eur J Nucl Med Mol Imaging 2006; 33: 311-318.
    CrossrefGoogle Scholar
  • 31 Yaromina A, Thames HD, Zhou X. et al. Radiobiological hypoxia, histological parameters of tumour microenvironment and local tumour control after fractionated irradiation. Radiother Oncol 2010; 96: 116-122.
    CrossrefGoogle Scholar
  • 32 Yaromina A, Zips D, Thames HD. et al. Pimonidazole labelling and response to fractionated irradiation of five human squamous cell carcinoma (hSCC) lines in nude mice. Radiother Oncol 2006; 81: 122-129.
    CrossrefGoogle Scholar
  • 33 Zimny M, Gagel B, Di Martino E. et al. FDG - a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer. Eur J Nucl Med Mol Imaging 2006; 33: 1426-1431.
    CrossrefGoogle Scholar