PET imaging of hypoxia using [18F]HX4: A phase i trial

Judith Van Loon*, 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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

98 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1663-1668
Number of pages6
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number9
Publication statusPublished - Aug 2010
Externally publishedYes

Bibliographical note

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


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