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PET imaging of hypoxia using [18F]HX4: a phase I trial

  • Judith van LoonEmail author
  • Marco H. M. Janssen
  • Michel Öllers
  • Hugo J. W. L. Aerts
  • Ludwig Dubois
  • Monique Hochstenbag
  • Anne-Marie C. Dingemans
  • Roy Lalisang
  • Boudewijn Brans
  • Bert Windhorst
  • Guus A. van Dongen
  • Hartmuth Kolb
  • James Zhang
  • Dirk De Ruysscher
  • Philippe Lambin
Short Communication

Abstract

Background and purpose

Noninvasive PET imaging of tumour hypoxia could help in the selection of those patients who could benefit from chemotherapy or radiation with specific antihypoxic treatments such as bioreductive drugs or hypoxic radiosensitizers. In this phase I trial, we aimed to determine the toxicity of [18F]HX4, a member of the 2-nitroimidazole family, at different dose levels. The secondary aim was to analyse image quality related to the HX4 dose and the timing of imaging.

Methods

Patients with a histologically proven solid cancer without curative treatment options were eligible for this study. A study design with two dose steps was used in which a single dose of a maximum of 222 MBq (step 1) or 444 MBq (step 2) [18F]HX4 was injected. Toxicity was scored on day 0 and on days 3 and 7 after injection, according to the CTCAE 3.0 scoring system. PET/CT images of the largest tumour site were acquired 30, 60 and 120 min after injection.

Results

Six patients with stage IV carcinoma were included, four with non-small-cell lung carcinoma, one with thymus carcinoma, and one with colon carcinoma. No toxicity was observed in any of the patients at either dose level. The median tumour to muscle ratio 120 min after injection was 1.40 (range 0.63–1.98).

Conclusion

The findings of this study showed that [18F]HX4 PET imaging for the detection of hypoxia is not associated with any toxicity. Imaging was successful; however, future trials are needed to determine the optimal image parameters.

Keywords

Hypoxia PET 18F-HX4 2-Nitroimidazoles Phase I trial 

Notes

Conflicts of interest

The unlabelled HX4 and its precursor were kindly provided by Siemens Molecular Imaging.

The authors acknowledge financial support from the Dutch Cancer Society (KWF fellowship granted to H.J.W.L.A.).

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Judith van Loon
    • 1
    Email author
  • Marco H. M. Janssen
    • 1
  • Michel Öllers
    • 1
  • Hugo J. W. L. Aerts
    • 1
  • Ludwig Dubois
    • 1
  • Monique Hochstenbag
    • 2
  • Anne-Marie C. Dingemans
    • 2
  • Roy Lalisang
    • 3
  • Boudewijn Brans
    • 4
  • Bert Windhorst
    • 5
  • Guus A. van Dongen
    • 5
    • 6
  • Hartmuth Kolb
    • 7
  • James Zhang
    • 7
  • Dirk De Ruysscher
    • 1
  • Philippe Lambin
    • 1
  1. 1.Department of Radiation Oncology (Maastro Clinic), GROW - School of Oncology and Developmental BiologyMaastricht University Medical CentreMaastrichtThe Netherlands
  2. 2.Department of PulmonologyMaastricht University Medical CentreMaastrichtThe Netherlands
  3. 3.Department of Medical OncologyMaastricht University Medical CentreMaastrichtThe Netherlands
  4. 4.Department of Nuclear MedicineMaastricht University Medical CentreMaastrichtThe Netherlands
  5. 5.Department of Nuclear Medicine and PET researchVU University Medical CentreAmsterdamThe Netherlands
  6. 6.Department of Otolaryngology/Head and Neck SurgeryVU University Medical CentreAmsterdamThe Netherlands
  7. 7.Siemens Molecular ImagingNorth WalesUSA

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