Study of LAT1 Expression in Brain Metastases: Towards a Better Understanding of the Results of Positron Emission Tomography Using Amino Acid Tracers.

Abstract

Positron emission tomography using radiolabeled amino acid (PET-AA) appears to be promising in distinguishing between recurrent tumour and radionecrosis in the follow-up of brain metastasis (BM). The amino acid transporter LAT1 and its cofactor CD98, which are involved in AA uptake, have never been investigated in BM. The aim of our study was to determine and compare the expression of LAT1 and CD98 in BM and in non-tumoral brain tissue (NT). The expression of LAT1 and CD98 were studied by immunohistochemistry in 67 BM, including 18 BM recurrences after radiotherapy, in 53 NT, and in 13 cases of patients with previously irradiated brain tumor and investigated by [18F] FDOPA-PET. LAT1 and CD98 expression were detected in 98.5% and 59.7% of BM respectively and were significantly associated with BM tissue as compared to NT (p<0.001). LAT1 expression in recurrent BM was significantly increased as compared to newly occurring BM. Ten cases investigated by [18F] FDOPA-PET corresponding to recurrent BM displayed significant [18F] FDOPA uptake and LAT1 overexpression whereas three cases corresponding to radionecrosis showed no or low uptake and LAT1 expression. LAT1 expression level and [18F] FDOPA uptake were significantly correlated. In conclusion, we hypothesized that BM may overexpress the AA transporter LAT1. We have shown that LAT1 overexpression was common in BM and was specific for BM as compared to healthy brain. These results could explain the specific BM uptake on PET-AA.