L-type amino acid transporter (LAT) 1 expression in 18F-FET-negative gliomas
Franziska Vettermann, Caroline Diekmann, Lorraine Weidner, Marcus Unterrainer, Bogdana Suchorska, Viktoria Ruf, Mario M. Dorostkar, Vera Wenter, Jochen Herms, Jörg‐Christian Tonn, Peter Bartenstein, Markus J. Riemenschneider, Nathalie L. Albert
Abstract
Abstract Background O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ( 18 F-FET) is a highly sensitive PET tracer for glioma imaging, and its uptake is suggested to be driven by an overexpression of the L-type amino-acid transporter 1 (LAT1). However, 30% of low- and 5% of high-grade gliomas do not present enhanced 18 F-FET uptake at primary diagnosis (“ 18 F-FET-negative gliomas”) and the pathophysiologic 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 18 F-FET-negative gliomas and to compare them to a matched group of 18 F-FET-positive gliomas. Forty newly diagnosed IDH -mutant astrocytomas without 1p/19q codeletion were evaluated (n = 20 18 F-FET-negative (tumour-to-background ratio (TBR) < 1.6), n = 20 18 F-FET-positive gliomas (TBR > 1.6)). LAT1 immunohistochemistry (IHC) was performed using SLC7A5/LAT1 antibody. The percentage of LAT1-positive tumour cells (%) and the staining intensity (range 0–2) were multiplied to an overall score (H-score; range 0–200) and correlated to PET findings as well as progression-free survival (PFS). Results IHC staining of LAT1 expression was positive in both, 18 F-FET-positive as well as 18 F-FET-negative gliomas. No differences were found between the 18 F-FET-negative and 18 F-FET-positive group with regard to percentage of LAT1-positive tumour cells, staining intensity or H-score. Interestingly, the LAT1 expression showed a significant negative correlation with the PFS ( p = 0.031), whereas no significant correlation was found for TBR max , neither in the overall group nor in the 18 F-FET-positive group only ( p = 0.651 and p = 0.140). Conclusion Although LAT1 is reported to mediate the uptake of 18 F-FET into tumour cells, the levels of LAT1 expression do not correlate with the levels of 18 F-FET uptake in IDH -mutant astrocytomas. In particular, the lack of tracer uptake in 18 F-FET-negative gliomas cannot be explained by a reduced LAT1 expression. A higher LAT1 expression in IDH -mutant astrocytomas seems to be associated with a short PFS. Further studies regarding mechanisms influencing the uptake of 18 F-FET are necessary.