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