Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Nov;42(12):1840-9.
doi: 10.1007/s00259-015-3100-z. Epub 2015 Jul 2.

Repeatability of hypoxia PET imaging using [¹⁸F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Affiliations
Clinical Trial

Repeatability of hypoxia PET imaging using [¹⁸F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Catharina M L Zegers et al. Eur J Nucl Med Mol Imaging. 2015 Nov.

Abstract

Purpose: Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [(18)F]HX4 in patients with head and neck and lung cancer.

Methods: Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [(18)F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUVmax and SUVmean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results: All parameters of [(18)F]HX4 uptake were significantly correlated between scans: SUVmax (r = 0.958, p < 0.001), SUVmean (r = 0.946, p < 0.001), TBRmax (r = 0.962, p < 0.001) and HV1.2 (r = 0.995, p < 0.001). The relative coefficients of repeatability were 15 % (SUVmean), 17 % (SUVmax) and 17 % (TBRmax). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65 ± 0.14.

Conclusion: Repeated hypoxia PET scans with [(18)F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [(18)F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

Keywords: HX4; Head and neck cancer; Hypoxia; Lung cancer; PET imaging.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Correlation and Bland-Altman plots (including 95 % confidence intervals) of the image parameters SUVmax and TBRmax
Fig. 2
Fig. 2
Example of voxel-wise analysis in a patient with head and neck cancer (patient 12). The axial, coronal and sagittal planes of the first and the rigidly registered second [18F]HX4 PET/CT scan are shown. The gross tumor volume is delineated. The bottom row shows the correlation plot, the Bland-Altman and the histogram plot of the voxels within the gross tumor volume
Fig. 3
Fig. 3
Examples of voxel-wise analysis in patients with lung cancer (patients 1 and 4). The axial plane of the CT scans with the gross tumor volumes delineated in yellow, the first [18F]HX4 PET scan, the rigidly registered second [18F]HX4 PET scan and the difference map from the two scans are shown

References

    1. Dubois LJ, Lieuwes NG, Janssen MH, Peeters WJ, Windhorst AD, Walsh JC, et al. Preclinical evaluation and validation of [18F]HX4, a promising hypoxia marker for PET imaging. Proc Natl Acad Sci U S A. 2011;108(35):14620–5. doi:10.1073/pnas.1102526108. - PMC - PubMed
    1. Chen L, Zhang Z, Kolb HC, Walsh JC, Zhang J, Guan Y. 18F-HX4 hypoxia imaging with PET/CT in head and neck cancer: a comparison with 18F-FMISO. Nucl Med Commun. 2012;33(10):1096–1102. doi: 10.1097/MNM.0b013e3283571016. - DOI - PubMed
    1. Wouters BG, van den Beucken T, Magagnin MG, Lambin P, Koumenis C. Targeting hypoxia tolerance in cancer. Drug Resist Updat. 2004;7(1):25–40. doi: 10.1016/j.drup.2003.12.004. - DOI - PubMed
    1. Walsh JC, Lebedev A, Aten E, Madsen K, Marciano L, Kolb HC. The clinical importance of assessing tumor hypoxia: relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid Redox Signal. 2014;21(10):1516–1554. doi: 10.1089/ars.2013.5378. - DOI - PMC - PubMed
    1. Wouters BG, Koritzinsky M, Chiu RK, Theys J, Buijsen J, Lambin P. Modulation of cell death in the tumor microenvironment. Semin Radiat Oncol. 2003;13(1):31–41. doi:10.1053/srao.2003.50004. - PubMed

Publication types

Substances

LinkOut - more resources