In-vivo quantification of hypoxic and metabolic status of NSCLC tumors using [18F]HX4 and [18F]FDG PET/CT imaging

Objective: Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non-small cell lung cancer (NSCLC). PET imaging is a non-invasive technique frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using FDG PET and hypoxia using HX4 PET imaging. Materials/Methods: FDG- and HX4-PET/CT images of 25 NSCLC patients were co-registered. At a global tumor-level, HX4 and FDG parameters were extracted from the gross-tumor-volume. The HX4-high fraction and high volume were defined using a tumor-to-blood ratio>1.4. This study used a SUV>50% of SUVmax for FDG-high fraction and high volume. We evaluated the spatial correlation between HX4 and FDG uptake within the tumor, to quantify the (mis)match between the volumes with high FDG and HX4 uptake. Results: At a tumor-level, significant correlations were observed between FDG and HX4 parameters. For the primary GTV, the HX4-high fraction was three times smaller compared to the FDG-high fraction. In 53% of the primary lesions, less than 1cm3 of the HX4-high-volume was outside the FDG-high volume; for 37% this volume was 1.9-12cm3. Remarkably, a distinct uptake pattern was observed in 11%, with large hypoxic volumes localized outside the FDG-high volume. Conclusion: Hypoxic tumor volumes are smaller than metabolic active volumes. Approximately half of the lesions showed a good spatial correlation between the PET tracers. In the other cases, a (partial)mismatch was observed. The addition of HX4-PET imaging has the potential to individualize patient treatment.status: publishe