Full kinetic modeling analysis of [18F]fluorocholine Positron Emission Tomography (PET) at initial diagnosis of high-grade glioma

•First PET study that characterizes the uptake of [18F]fluorocholine in human gliomas through a full tracer kinetic modeling approach.•High-grade glioma time-activity curves show a rapid rise of [18F]fluorocholine uptake followed by a plateau-like shape.•[18F]fluorocholine uptake in high-grade gliomas is explained by a near-irreversible two-tissue compartment model.•Good correlation between SUV-based measures of [18F]fluorocholine and the absolute rate constants from kinetic modeling (K1 and Ki).•The study validates and provides a rational basis for the use of [18F]fluorocholine PET static measures in the clinical setting. The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808–0.861), SUVmean (r = 0.794–0.851) and TBR (r = 0.643–0.784), p