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EJNMMI Research
Published in: EJNMMI Research 1/2021

Open Access 01-12-2021 | Astrocytoma | Original research

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

Authors: Franziska J. Vettermann, Caroline Diekmann, Lorraine Weidner, Marcus Unterrainer, Bogdana Suchorska, Viktoria Ruf, Mario Dorostkar, Vera Wenter, Jochen Herms, Jörg-Christian Tonn, Peter Bartenstein, Markus J. Riemenschneider, Nathalie L. Albert

Published in: EJNMMI Research | Issue 1/2021

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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.
Appendix
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Metadata
Title
L-type amino acid transporter (LAT) 1 expression in 18F-FET-negative gliomas
Authors
Franziska J. Vettermann
Caroline Diekmann
Lorraine Weidner
Marcus Unterrainer
Bogdana Suchorska
Viktoria Ruf
Mario Dorostkar
Vera Wenter
Jochen Herms
Jörg-Christian Tonn
Peter Bartenstein
Markus J. Riemenschneider
Nathalie L. Albert
Publication date
01-12-2021
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2021
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-021-00865-9

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