Comparison between [(68)Ga]Ga-PSMA-617 and [(18)F]FET PET as Imaging Biomarkers in Adult Recurrent Glioblastoma

The aim of this prospective clinical study was to evaluate the potential of the prostate specific membrane antigen (PSMA) targeting ligand, [(68)Ga]-PSMA–Glu–NH–CO–NH–Lys-2-naphthyl-L-Ala-cyclohexane-DOTA ([(68)Ga]Ga-PSMA-617) as a positron emission tomography (PET) imaging biomarker in recurrent glioblastoma patients. Patients underwent [(68)Ga]Ga-PSMA-617 and O-(2-[(18)F]-fluoroethyl)-L-tyrosine ([(18)F]FET) PET scans on two separate days. [(68)Ga]Ga-PSMA-617 tumour selectivity was assessed by comparing tumour volume delineation and by assessing the intra-patient correlation between tumour uptake on [(68)Ga]Ga-PSMA-617 and [(18)F]FET PET images. [(68)Ga]Ga-PSMA-617 tumour specificity was evaluated by comparing its tumour-to-brain ratio (TBR) with [(18)F]FET TBR and its tumour volume with the magnetic resonance imaging (MRI) contrast-enhancing (CE) tumour volume. Ten patients were recruited in this study. [(68)Ga]Ga-PSMA-617-avid tumour volume was larger than the [(18)F]FET tumour volume (p = 0.063). There was a positive intra-patient correlation (median Pearson r = 0.51; p < 0.0001) between [(68)Ga]Ga-PSMA-617 and [(18)F]FET in the tumour volume. [(68)Ga]Ga-PSMA-617 had significantly higher TBR (p = 0.002) than [(18)F]FET. The [(68)Ga]Ga-PSMA-617-avid tumour volume was larger than the CE tumour volume (p = 0.0039). Overall, accumulation of [(68)Ga]-Ga-PSMA-617 beyond [(18)F]FET-avid tumour regions suggests the presence of neoangiogenesis in tumour regions that are not overly metabolically active yet. Higher tumour specificity suggests that [(68)Ga]-Ga-PSMA-617 could be a better imaging biomarker for recurrent tumour delineation and secondary treatment planning than [(18)F]FET and CE MRI.