Abstract
PURPOSE: Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [(68)Ga]Ga-PSMA-11 or [(18)F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression. METHODS: Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled. All patients underwent PSMA PET combined with computer tomography (CT) with either [(68)Ga]Ga-PSMA-11 (cohort I, 20 patients) or [(18)F]PSMA-1007 (cohort II, 15 patients) followed by radical prostatectomy. Specimens were scanned by ex-vivo CT and histologically prepared. On digitized whole-mount prostate sections, PCa areas with different morphologies were manually defined and H-Score of immunohistochemical PSMA expression was calculated with assistance by artificial intelligence (AI). PCa areas with similar H-Score were unified in segmentation on ex-vivo CT. After co-registration on PSMA PET-CT, Spearman's coefficients of PSMA expression to mean and maximum standardized uptake value (SUV(mean) and SUV(max)) were calculated. Furthermore, the agreement of the co-registered tumour areas to gross tumour volume (GTV) in PSMA PET was analysed. RESULTS: Thirty-two patients were included in the final analysis. For histological PCa areas, immunohistochemical PSMA expression correlated significantly to SUV(mean) and SUV(max) (p < 0.001, p = 0.001). An approximate linear correlation between H-Score and SUV(mean) / SUV(max) was found for tumour areas larger than 400 μm² in histology (p < 0.001). Tumour areas with strong PSMA expression showed a significantly larger overlap to GTV in PSMA PET after co-registration than tumour areas with very low PSMA expression (p < 0.01). No significant differences were found between the two tracer cohorts (p = 0.72). CONCLUSION: PSMA PET with both [(68)Ga]Ga-PSMA-11 or [(18)F]PSMA-1007 is able to detect changes in histological PSMA expression within PCa lesions allowing biologically targeted radiotherapy.