Dubois, Ludwig J.;
Lieuwes, Natasja G.;
Janssen, Marco H. M.;
Peeters, Wenny J. M.;
Windhorst, Albert D.;
Walsh, Joseph C.;
Kolb, Hartmuth C.;
Öllers, Michel C.;
Bussink, Johan;
van Dongen, Guus A. M. S.;
van der Kogel, Albert;
Lambin, Philippe
Preclinical evaluation and validation of [ 18 F]HX4, a promising hypoxia marker for PET imaging
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Preclinical evaluation and validation of [ 18 F]HX4, a promising hypoxia marker for PET imaging
Contributor:
Dubois, Ludwig J.;
Lieuwes, Natasja G.;
Janssen, Marco H. M.;
Peeters, Wenny J. M.;
Windhorst, Albert D.;
Walsh, Joseph C.;
Kolb, Hartmuth C.;
Öllers, Michel C.;
Bussink, Johan;
van Dongen, Guus A. M. S.;
van der Kogel, Albert;
Lambin, Philippe
imprint:
Proceedings of the National Academy of Sciences, 2011
Published in:Proceedings of the National Academy of Sciences
Language:
English
DOI:
10.1073/pnas.1102526108
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
<jats:p>
Hypoxia has been shown to be an important microenvironmental parameter influencing tumor progression and treatment efficacy. Patient guidance for hypoxia-targeted therapy requires evaluation of tumor oxygenation, preferably in a noninvasive manner. The aim of this study was to evaluate and validate the uptake of [
<jats:sup>18</jats:sup>
F]HX4, a novel developed hypoxia marker for PET imaging. A heterogeneous accumulation of [
<jats:sup>18</jats:sup>
F]HX4 was found within rat rhabdomyosarcoma tumors that was significantly (
<jats:italic>P</jats:italic>
< 0.0001) higher compared with the surrounding tissues, with temporal increasing tumor-to-blood ratios reaching a plateau of 7.638 ± 0.926 and optimal imaging properties 4 h after injection. [
<jats:sup>18</jats:sup>
F]HX4 retention in normal tissues was found to be short-lived, homogeneous and characterized by a fast progressive temporal clearance. Heterogeneity in [
<jats:sup>18</jats:sup>
F]HX4 tumor uptake was analyzed based on 16 regions within the tumor according to the different orthogonal planes at the largest diameter. Validation of heterogeneous [
<jats:sup>18</jats:sup>
F]HX4 tumor uptake was shown by a strong and significant relationship (
<jats:italic>r</jats:italic>
= 0.722;
<jats:italic>P</jats:italic>
< 0.0001) with the hypoxic fraction as calculated by the percentage pimonidazole-positive pixels. Furthermore, a causal relationship with tumor oxygenation was established, because combination treatment of nicotinamide and carbogen resulted in a 40% reduction (
<jats:italic>P</jats:italic>
< 0.001) in [
<jats:sup>18</jats:sup>
F]HX4 tumor accumulation whereas treatment with 7% oxygen breathing resulted in a 30% increased uptake (
<jats:italic>P</jats:italic>
< 0.05). [
<jats:sup>18</jats:sup>
F]HX4 is therefore a promising candidate for noninvasive detection and evaluation of tumor hypoxia at a macroscopic level.
</jats:p>