${}^{18}$f-fluoroethyl-tyrosine uptake is correlated with amino acid transport and neovascularization in treatment-naive glioblastomas

To investigate the in vivo correlation between ${}^{18}$F-fluoroethyl-tyrosine (18F-FET) uptake and amino acid transporter expression and vascularization in treatment-naive glioblastomas. A total of 43 stereotactic biopsies were obtained from 13 patients with suspected glioblastoma prior to therapy. All patients underwent a dynamic ${}^{18}$F-FET PET/MRI scan before biopsy. Immunohistochemistry was performed using antibodies against SLC7A5 (amino acid transporter), MIB-1 (Ki67, proliferation), CD31 (vascularization) and CA-IX (hypoxia). The intensity of staining was correlated with ${}^{18}$F-FET uptake and the dynamic ${}^{18}$F-FET uptake slope at the biopsy target point. In all patients, the final diagnosis was IDH-wildtype glioblastoma, WHO grade IV. Static ${}^{18}$F-FET uptake was significantly correlated with SLC7A5 staining (r = 0.494, p = 0.001). While the dynamic ${}^{18}$F-FET uptake slope did not show a significant correlation with amino acid transporter expression, it was significantly correlated with the number of CD31-positive vessels (r = −0.350, p = 0.031), which is line with earlier results linking ${}^{18}$F-FET kinetics with vascularization and perfusion. Besides, static ${}^{18}$F-FET uptake also showed correlations with CA-IX staining (r = 0.394, p = 0.009) and CD31 positivity (r = 0.410, p = 0.006). While the correlation between static ${}^{18}$F-FET uptake and SLC7A5 staining was confirmed as significant in multivariate analysis, this was not the case for the correlation with CD31 positivity, most likely because of the lower effect size and the relatively low number of samples. No significant correlation between ${}^{18}$F-FET uptake and Ki67 proliferation index was observed in our cohort. Our results support the findings of preclinical studies suggesting that specific ${}^{18}$F-FET uptake in glioblastomas is mediated by amino acid transporters. As proposed previously, dynamic ${}^{18}$F-FET parameters might be more influenced by perfusion and therefore related to properties of the tumour neovascularization.