Skip to main content

Advertisement

Log in

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

  • Short Communication
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem 2009;107:1053–62

    Article  CAS  PubMed  Google Scholar 

  2. Wouters BG, Weppler SA, Koritzinsky M, Landuyt W, Nuyts S, Theys J, et al. Hypoxia as a target for combined modality treatments. Eur J Cancer 2002;38:240–57.

    Article  CAS  PubMed  Google Scholar 

  3. Rasey JS, Grunbaum Z, Magee S, Nelson NJ, Olive PL, Durand RE, et al. Characterization of radiolabeled fluoromisonidazole as a probe for hypoxic cells. Radiat Res 1987;111:292–304.

    Article  CAS  PubMed  Google Scholar 

  4. 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;50:2209–24.

    Article  PubMed  Google Scholar 

  5. Nunn A, Linder K, Strauss HW. Nitroimidazoles and imaging hypoxia. Eur J Nucl Med 1995;22:265–80.

    Article  CAS  PubMed  Google Scholar 

  6. Krohn KA, Link JM, Mason RP. Molecular imaging of hypoxia. J Nucl Med 2008;49 Suppl 2:129S–48S.

    Article  CAS  PubMed  Google Scholar 

  7. Piert M, Machulla HJ, Picchio M, Reischl G, Ziegler S, Kumar P, et al. Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J Nucl Med 2005;46:106–13.

    PubMed  Google Scholar 

  8. Ollers M, Bosmans G, van Baardwijk A, Dekker A, Lambin P, Teule J, et al. The integration of PET-CT scans from different hospitals into radiotherapy treatment planning. Radiother Oncol 2008;87:142–6.

    Article  PubMed  Google Scholar 

  9. Dierckx RA, Van de Wiele C. FDG uptake, a surrogate of tumour hypoxia? Eur J Nucl Med Mol Imaging 2008;35:1544–9.

    Article  CAS  PubMed  Google Scholar 

  10. van Baardwijk A, Dooms C, van Suylen RJ, Verbeken E, Hochstenbag M, Dehing-Oberije C, et al. The maximum uptake of (18)F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1alpha and GLUT-1 in non-small cell lung cancer. Eur J Cancer 2007;43:1392–8.

    Article  PubMed  Google Scholar 

Download references

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.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Judith van Loon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Loon, J., Janssen, M.H.M., Öllers, M. et al. PET imaging of hypoxia using [18F]HX4: a phase I trial. Eur J Nucl Med Mol Imaging 37, 1663–1668 (2010). https://doi.org/10.1007/s00259-010-1437-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-010-1437-x

Keywords

Navigation