Lack of LAT1 and CD98hc Expression on Tumor Cells of Diffuse Glioma: Revisiting the Molecular Basis for Amino Acid PET Imaging and Theranostics

It is assumed that amino acid PET positivity of gliomas corresponds to tracer uptake by tumor cells via the amino acid transporter heterodimer CD98, consisting of a light (LAT1) and heavy subunit (CD98hc), but correlative studies of human tumor tissue samples and PET imaging are largely lacking. Methods: We evaluated a series of 31 patients with diffuse glioma (18 IDH-mutant, 13 IDH-wild type), of whom preoperative amino acid PET images and corresponding tumor tissue samples were available. LAT1 and CD98hc expression were immunohistochemically assessed and correlated to amino acid PET tracer uptake parameters. Results: LAT1 and CD98hc subunits were strongly and almost exclusively expressed on endothelial cells, with most tumor cells lacking immunostaining. There was no correlation of LAT1 or CD98hc expression with amino acid PET uptake parameters. Conclusion: Further studies to clarify the molecular basis of amino acid tracer uptake in diffuse glioma are warranted.