[18F] FDOPA standardized uptake values of brain tumors are not exclusively dependent on LAT1 expression

Abstract

[18F]-FDOPA is a labeled amino acid (AA) analog used for positron emission tomography (PET) which is gaining increasing interest in the evaluation of brain tumors (BT). The AA-transporter LAT1 has been shown to be involved in [18F]-FDOPA uptake. The aim of this study was to determine whether the [18F]-FDOPA uptake was correlated with level of LAT1 expression in BT. Twenty-eight BT (including 19 gliomas and 9 metastases) were investigated by [18F]-FDOPA-PET prior to surgery and by anti-LAT1 immunohistochemistry on surgical specimens. The quantitative [18F]-FDOPA measured parameters were SUVmax, SUVmean and SUVpeak. LAT1 expression was quantified using a score (0 to 400). A significant [18F]-FDOPA uptake was associated with a LAT1 score ≥ 100 (p = 0.02) but there was no linear correlation between intensity of [18F]-FDOPA uptake and score of LAT1 expression whatever the parameters considered. LAT1 expression alone is not sufficient to explain variation of intensity of [18F]-FDOPA uptake in BT.

Effects of Photons Irradiation on 18F-FET and 18F-DOPA Uptake by T98G Glioblastoma Cells

“…In addition, it is not possible to discriminate in this group patients who were free of disease versus recurrence in a short time. On the contrary, Dadone and colleagues did not find any significant correlation between the interval from radiotherapy to PET scan in terms of SUV (Dadone-Montaudié et al, 2017).…”

“…Nonetheless, the intensity of 18 F-DOPA uptake is not directly correlated with the level of LAT-1 expression. A minimal expression of LAT1 is required for 18 F-DOPA uptake, but this amount is not linearly related to the histochemical score of LAT-1 expression, suggesting that the balance between influx and efflux is not sufficient to understand the mechanism of uptake and retention (Dadone-Montaudié et al, 2017).…”

Update on amino acid PET of brain tumours

“…According to previous findings, the transport of these amino acids occurs predominantly via the transport system L for large neutral amino acids namely the subtypes LAT1 and LAT2 although other transport systems may play a role [20][21][22][23]. The visualization of brain tumors with MET, FET and FDOPA is very similar [24][25][26] but in contrast to MET and FDOPA, FET shows a tumor-type specific tracer kinetics, which can be helpful in differential diagnosis [27-29, 26, 30].…”

The Emerging Role of Amino Acid PET in Neuro-Oncology

“…Compromise of the BBB by tumor growth does not appear to be a requirement for amino acid tracer permeability [31,32]. The intracellular uptake of amino acid tracers by the tumor cells is an active process facilitated by the L (large) transport system with subtypes LAT1 and LAT2 and is, therefore, more specific in reporting on live proliferating cells rather than structural changes [33,34,35,36]. This is further evidenced by dexamethasone or antiangiogenic treatment with bevacizumab not affecting amino acid uptake by brain tumors [37,38].…”