Estimation of split renal function using [18F]-flotufolastat PET/CT compared with [68Ga]-PSMA-11 and [99mTc]-MAG3 scintigraphy

Physiological prostate-specific membrane antigen (PSMA) expression in renal proximal tubules results in radiopharmaceutical uptake in PSMA-PET, suggesting the potential to assess renal function. To evaluate split renal function derived from [18F]F-flotufolastat ([18F]F-rhPSMA-7.3) PET/CT and to systematically compare its performance with [68Ga]Ga-PSMA-11 PET/CT and the reference standard [99mTc]Tc-MAG3 scintigraphy, we retrospectively analyzed 302 patients with metastatic castration-resistant prostate cancer undergoing PSMA-PET/CT using either [18F]F-flotufolastat (n = 221) or [68Ga]Ga-PSMA-11 (n = 81), along with [99mTc]Tc-MAG3 scintigraphy, prior to PSMA radioligand therapy. SRF was calculated from PSMA-PET/CT using mean standardized uptake values and CT-derived renal volumes. SRF was calculated from [99mTc]Tc-MAG3 using standard integral analysis. SRF derived from PSMA-PET/CT ([18F]F-flotufolastat and [68Ga]Ga-PSMA-11) was correlated with split renal function obtained from [99mTc]Tc-MAG3 scintigraphy on a side-specific basis using Pearson correlation and Bland–Altman analysis. Receiver operating characteristic (ROC) analyses were performed to evaluate diagnostic performance for detecting impaired renal function (SRF ≤ 25% and ≤ 40%). A PET-based accumulation index (ACI) was explored in relation to estimated glomerular filtration rate (eGFR) in an exploratory, tracer-specific analysis. Strong correlations were found between PET-SRF and [99mTc]Tc-MAG3-SRF (r = 0.88 for [18F]F-flotufolastat, r = 0.85 for [68Ga]Ga-PSMA-11; both p < 0.0001). Bland–Altman analysis showed a smaller mean bias and narrower limits of agreement for [18F]F-flotufolastat (-0.56%; -11.88% to + 10.75%) compared with [68Ga]Ga-PSMA-11 (-1.18%; -15.3% to + 12.95%), with 92% versus 83% of values within ± 10%, respectively. ROC analysis confirmed excellent accuracy for identifying [99mTc]Tc-MAG3-SRF ≤ 25% (area under the curve [AUC] = 0.997 for [18F]F-flotufolastat; AUC = 0.942 for [68Ga]Ga-PSMA-11). No significant association was observed between ACI and eGFR for either radiopharmaceutical ([18F]F-flotufolastat: Spearman’s ρ = 0.056, p = 0.414; [68Ga]Ga-PSMA-11: Spearman’s ρ = − 0.071, p = 0.536). PSMA-PET/CT provides reliable estimates of SRF, with [18F]F-flotufolastat showing slightly superior agreement with [99mTc]Tc-MAG3 scintigraphy. This may potentially eliminate the need for additional renal scintigraphy for SRF assessment in the future and may simplify workflows and reduce patient burden.