Head-to-head comparison of [¹⁸F]F-PSMA-1007 PET/CT and [⁶⁸Ga]Ga-PSMA-11 PET/CT for intraprostatic tumour detection and localisation using histopathology as reference: A prospective single-centre diagnostic accuracy study

Abstract Purpose Prostate-specific membrane antigen (PSMA) PET has emerged as a sensitive imaging modality for prostate cancer (PC), but its role in intraprostatic tumour localisation relative to multiparametric MRI (mpMRI) and differences between [¹⁸F]- and [⁶⁸Ga]-PSMA ligands remain unclear. This study compared the diagnostic performance of [¹⁸F]F-PSMA-1007 PET/CT, [⁶⁸Ga]Ga-PSMA-11 PET/CT, and mpMRI for intraprostatic tumour localisation and detection of clinically significant prostate cancer (csPC). Methods In this prospective single-centre study, patients with biopsy-proven high-risk PC undergoing radical prostatectomy were recruited. All patients underwent [¹⁸F]F-PSMA-1007 PET/CT and [⁶⁸Ga]Ga-PSMA-11 PET/CT. Following a protocol amendment, mpMRI was added as a secondary exploratory imaging modality and performed in a subset of patients prior to surgery. Histopathology was the reference standard; csPC was defined as ≥ISUP3 or ISUP2 with tertiary Gleason 5 pattern. Diagnostic performance was assessed on a per-patient and per-region basis, dividing the prostate into sextants and using mixed regression models to account for clustering. Secondary analyses evaluated the detection of pathological features beyond the prostate, including extraprostatic extension (EPE) and seminal vesicle invasion (SVI). Results Fifty patients were included in the analysis of PSMA PET/CT, and 45 patients had mpMRI. At the patient level, [¹⁸F]F-PSMA-1007 PET/CT, [⁶⁸Ga]Ga-PSMA-11 PET/CT and mpMRI demonstrated sensitivities of 98%, 100%, and 96%, respectively, for the detection of csPC, with corresponding diagnostic accuracies of 96%, 98%, and 93%, respectively. Of 300 sextants, 205 contained csPC. [¹⁸F]F-PSMA-1007 PET/CT identified csPC in 143/300 sextants (accuracy: 69.8%, 95%CI 64.0–75.6). [⁶⁸Ga]Ga-PSMA-11 PET/CT detected csPC in 136/300 sextants (accuracy: 67.8%, 95%CI 62.3–73.4). mpMRI identified csPC in 89/270 sextants (accuracy: 62.9%, 95%CI 56.3–69.4). PSMA PET ligands showed significantly higher sensitivity than mpMRI ( p < 0.001), whereas mpMRI demonstrated higher specificity ( p = 0.002). No significant differences were observed between [¹⁸F]F-PSMA-1007 and [⁶⁸Ga]Ga-PSMA-11. Detection of pathological features of local tumour extension was limited across all modalities. Sensitivity for EPE was 12%, 23%, and 9%, and sensitivity for SVI was 30%, 30%, and 14% for [¹⁸F]F-PSMA-1007 PET/CT, [⁶⁸Ga]Ga-PSMA-11 PET/CT, and mpMRI, respectively. Conclusion PSMA PET/CT ligands provide higher sensitivity than mpMRI for intraprostatic tumour localisation, while no statistically significant differences in diagnostic performance were detected between [¹⁸F]- and [⁶⁸Ga]-PSMA ligands in this cohort. These findings support the potential complementary role of PSMA PET and mpMRI for preoperative intraprostatic tumour localisation in high-risk PC.