L-type amino acid transporter (LAT) 1 expression in 18F-FET-negative gliomas

Springer Science and Business Media LLC - Tập 11 Số 1
Franziska Vettermann1, Caroline Diekmann1, Lorraine Weidner2, Marcus Unterrainer3, Bogdana Suchorska4, Viktoria Ruf5, Mario M. Dorostkar5, Vera Wenter1, Jochen Herms5, Jörg‐Christian Tonn4, Peter Bartenstein6, Markus J. Riemenschneider2, Nathalie L. Albert6
1Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany
2Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany
3Department of Radiology, University Hospital of Munich, LMU Munich, Munich, Germany
4Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany
5Center for Neuropathology, University Hospital of Munich, LMU Munich, Munich, Germany
6German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany

Tóm tắt

Abstract Background O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-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 18F-FET uptake at primary diagnosis (“18F-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 18F-FET-negative gliomas and to compare them to a matched group of 18F-FET-positive gliomas. Forty newly diagnosed IDH-mutant astrocytomas without 1p/19q codeletion were evaluated (n = 20 18F-FET-negative (tumour-to-background ratio (TBR) < 1.6), n = 20 18F-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, 18F-FET-positive as well as 18F-FET-negative gliomas. No differences were found between the 18F-FET-negative and 18F-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 TBRmax, neither in the overall group nor in the 18F-FET-positive group only (p = 0.651 and p = 0.140). Conclusion Although LAT1 is reported to mediate the uptake of 18F-FET into tumour cells, the levels of LAT1 expression do not correlate with the levels of 18F-FET uptake in IDH-mutant astrocytomas. In particular, the lack of tracer uptake in 18F-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 18F-FET are necessary.

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