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