Comparison of L-type amino acid transporters 1 (LAT1) in 18F-FET-negative vs. FET positive gliomas

401 Introduction: O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) is a highly sensitive tracer for glioma imaging and its uptake in gliomas is suggested to be driven by an overexpression of L-type amino-acid transporter 1 (LAT1). However, 30% of low- and 5% of high-grade glioma do not present enhanced FET-uptake at primary diagnosis (FET-negative) and the pathophysiological basis for this phenomenon remains unclear. The aim of this study was to determine the expression of LAT1 in a homogeneous group of newly diagnosed 18F-FET-positive and 18F-FET-negative IDH 1/2-mutant WHO grade II and III gliomas without 1p/19q codeletion. Methods: Newly diagnosed WHO grade II and III gliomas (IDH 1/2-mutant, no 1p/19q codeletion) were classified as either FET-negative (tumor-to-background ratio (TBR) 1.6). LAT1 immunohistochemistry (IHC) was performed using a SLC7A5/LAT1 antibody; the percentage of LAT1-positive tumor cells (0, 75%=4) and the staining intensity (range: 0-3) was multiplied to an overall score (range 0-12) and correlated with the PET findings. Results: IHC is finalized in 18 cases (50 cases are currently being analysed). 10 gliomas were FET-positive (4 WHO grade II, 6 WHO grade III), 8 were FET-negative (4 WHO grade II, 4 WHO grade III). FET-positive gliomas showed a significantly higher median amount of LAT1-positive tumor cells and a higher overall score than FET-negative gliomas (positive tumor cells=2.5 vs 1.5; p=0.034; overall score=4.5 vs 2.0; p=0.021). The staining intensity showed a trend towards higher values in FET-positive cases (2 vs 1; p=0.075). The TBRmax showed a positive correlation with the amount of positive tumor cells (r=0.49; p=0.036) as well as the overall score (r=0.50; p=0.041). Discussion: Our preliminary data support the hypothesis that LAT1 might play a major role in the process of FET-uptake in gliomas. FET-negativity of gliomas seems to be associated with a significantly smaller amount of LAT1-positive tumor cells compared to FET-positive gliomas within the same molecular genetic entity. The trend towards a lower LAT1-staining intensity in FET-negative tumor cells may further indicate a lower expression of LAT1 in the individual glioma cell, which is currently being evaluated in a significantly lager set of patients (n=68).