P04.26 In vitro and in vivo evaluation of the LAT1 PET tracer 2-[18F]FELP in comparison to [18F]FET and [18F]FDG
Authors: J. Verhoeven, J. Bolcaen, K. Kersemans, V. De Meulenaere, K. Deblaere, J. Kalala, C. Van den Broecke, C. Vanhove, I. Goethals, F. De Vos
Journal: Neuro-Oncology (2017)

Introduction: Metabolic imaging of gliomas using 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and O-(2-(18F]fluoroethyl)-L-tyrosine ([18F]FET) Positron Emission Tomography (PET) has been widely evaluated. However, the high uptake of [18F]FDG in the normal brain limits its sensitivity for brain tumor detection and the uptake mechanism of [18F]FET is not yet fully clarified. A relatively low affinity for the L-type Amino Acid Transporter 1 (LAT1) has been assumed for [18F]FET. The aim of this study was to evaluate a novel in-house made and more LAT1 selective amino acid PET tracer, 2-[18F]fluoroethyl-L-phenylalanine (2-[18F]FELP), in vitro and in vivo. Methods: To determine the selectivity for the LAT1 transporter the in vitro 2-[18F]FELP uptake was studied in the presence of Na+, the system L inhibitor 2-aminobicycloheptane-2-carboxylic acid (BCH) or the system A inhibitor methylaminoisobutyric acid (MeAiB). Six female NIH-Foxn1rnu rats were inoculated with ± 20 000 F98 tumor cells in the right frontal lobe. Tumor growth was evaluated 8 days postinoculation (p.i.) using T2W and contrast-enhanced T1W sequences on a 7T MRI system. If tumor was confirmed, dynamic 2-[18F]FELP, [18F]FET and [18F]FDG PET images were acquired on three consecutive days (day 13, 14 and 15 p.i.). The acquisition time was 120 min for both dynamic amino acid PET scans and 60 min for the dynamic [18F]FDG PET ([18F]FDGearly). In addition, a static 30 min [18F]FDG PET was acquired 240 min p.i. ([18F]FDGlate). Standardized uptake values (SUVmean and SUVmax) and tumor to background ratios (TBRmean and TBRmax) were calculated and compared using the Mann–Whitney U test. A probability value < 0.05 was considered statistically significant. Results: In vivo The uptake of 2-[18F]FELP and [18F]FET was 32% and 56% higher in presence of Na+ ions, respectively. BCH inhibited the 2-[18F]FELP uptake by >99% while the [18F]FET uptake was inhibited for 96%. The [18F]FET and 2-[18F]FELP uptake was reduced to 9% and 5% respectively by MeAiB. In vivo GB characteristics were confirmed on hematoxylin and eosin staining. The uptake of [18F]FDG was clearly higher in normal brain tissue compared to the amino acid PET. No significantly different TBR and SUV values were found between 2-[18F]FELP and [18F]FET PET. Significant differences were observed between 2-[18F]FELP and [18F]FDGearly (TBRmean, TBRmax, SUVmean), [18F]FET and [18F]FDGearly (TBRmean, TBRmax), [18F]FET and [18F]FDGlate (TBRmean, TBRmax), [18F]FDGearly and [18F]FDGlate (TBRmax, SUVmean). Conclusion: The in vitro data suggests that 2-[18F]FELP is more selective for the LAT1 transporter than [18F]FET. There were no significantly different TBRmean, TBRmax, SUVmean tumor and SUVmax tumor values in comparison to [18F]FET. However higher TBRs were found compared to [18F]FDG PET. Based on our results, 2-[18F]FELP PET is a promising new tracer for imaging high-grade glioma.