Defining the hypoxic target volume based on positron emission tomography for image guided radiotherapy – the influence of the choice of the reference region and conversion function
Creators: name: Lindblom, Emely
name: Dasu, Alexandru
name: Uhrdin, Johan
name: Even, Aniek
name: Elmpt, Wouter Van
name: Lambin, Philippe
name: Wersäll, Peter
name: Toma-Dasu, Iuliana
Publisher: name: Taylor & Francis
Year: 2017
Subjects: subject: Biophysics
subject: Space Science
subject: 29999 Physical Sciences not elsewhere classified
subject: FOS: Physical sciences
subject: FOS: Physical sciences
subject: Medicine
subject: Cell Biology
subject: Physiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Ecology
subject: Cancer

description: <b>Background:</b> Hypoxia imaged by positron emission tomography (PET) is a potential target for optimization in radiotherapy. However, the implementation of this approach with respect to the conversion of intensities in the images into oxygenation and radiosensitivity maps is not straightforward. This study investigated the feasibility of applying two conversion approaches previously derived for <sup>18</sup>F-labeled fluoromisonidazole (<sup>18</sup>F-FMISO)-PET images for the hypoxia tracer <sup>18</sup>F-flortanidazole (<sup>18</sup>F-HX4). <b>Material and methods:</b> Ten non-small-cell lung cancer patients imaged with <sup>18</sup>F-HX4 before the start of radiotherapy were considered in this study. PET image uptake was normalized to a well-oxygenated reference region and subsequently linear and non-linear conversions were used to determine tissue oxygenations maps. These were subsequently used to delineate hypoxic volumes based partial oxygen pressure (pO<sub>2</sub>) thresholds. The results were compared to hypoxic volumes segmented using a tissue-to-background ratio of 1.4 for <sup>18</sup>F-HX4 uptake. <b>Results:</b> While the linear conversion function was not found to result in realistic oxygenation maps, the non-linear function resulted in reasonably sized sub-volumes in good agreement with uptake-based segmented volumes for a limited range of pO<sub>2</sub> thresholds. However, the pO<sub>2</sub> values corresponding to this range were significantly higher than what is normally considered as hypoxia. The similarity in size, shape, and relative location between uptake-based sub-volumes and volumes based on the conversion to pO<sub>2</sub> suggests that the relationship between uptake and pO<sub>2</sub> is similar for <sup>18</sup>F-FMISO and <sup>18</sup>F-HX4, but that the model parameters need to be adjusted for the latter. <b>Conclusions:</b> A non-linear conversion function between uptake and oxygen partial pressure for <sup>18</sup>F-FMISO-PET could be applied to <sup>18</sup>F-HX4 images to delineate hypoxic sub-volumes of similar size, shape, and relative location as based directly on the uptake. In order to apply the model for e.g., dose-painting, new parameters need to be derived for the accurate calculation of dose-modifying factors for this tracer.