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. 2026 Feb 3;16(1):36.
doi: 10.1186/s13550-026-01385-0.

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

Michael Christian Marius Gammel  1 , Charlotte Olufs  2 , Kimberley Hansen  2 , Julia Brosch-Lenz  2 , Matthias Heck  3 , Wolfgang A Weber  2   4 , Matthias Eiber  2   4 , Isabel Rauscher  2   4
Affiliations

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

Michael Christian Marius Gammel et al. EJNMMI Res. .

Abstract

Background: 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.

Results: 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).

Conclusion: 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.

Keywords: PET/CT; PSMA; Prostate cancer; Split renal function; [99mTc]Tc-MAG3.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All patients provided written informed consent for the clinical examination and reported investigations were conducted in accordance with the Declaration of Helsinki and with national regulations. The local ethics committee approved the retrospective analysis (permits: 2019-99_2-S-SR, updated on May 31, 2023). Consent for publication: Not applicable. Competing interests: Isabel Rauscher and Matthias Eiber received consulting fees, research funding and travel support from Blue Earth Diagnostics Ltd. Outside the submitted work, Matthias Eiber reports fees from Novartis/AAA (consultant, speaker), Telix (consultant), Bayer (consultant, research funding), RayzeBio (consultant), Point Biopharma (consultant), Eckert-Ziegler (speaker), ABX GmbH (speaker), and Janssen Pharmaceuticals (consultant, speakers bureau); Parexel (image review) and Bioclinica (image review; and a patent application for rhPSMA. He and other inventors are entitled to royalties on sales of [18F]F-flotufolastat. Wolfgang A Weber reports research support fees from Blue Earth Diagnostics Ltd, ITM, Novartis, and Pentixapharm. He has also acted as a consultant for these companies. There are no other conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
(A) [99mTc]Tc-MAG3 scintigraphy acquired 20 min post-injection after administration of 112 MBq, with the corresponding renogram curves (B) of both kidneys shown below. (C) Coronal PET/CT images acquired 62 min post-injection after administration of 340 MBq [18F]F-flotufolastat are shown on the right. Split renal function calculated from both modalities shows concordant results, with MAG3 scintigraphy indicating a functional contribution of 94% for the left kidney and 6% for the right kidney, and PET-based analysis showing 91% and 9%, respectively 18F = Fluorine-18; MAG3 = mercapto-acetyltriglycine; PET = positron emission tomography; SRF = split renal function; ⁹⁹ᵐTc = Technetium-99 m
Fig. 2
Fig. 2
Bland–Altman plots comparing PSMA-PET-derived SRF with [99mTc]Tc-MAG3-based SRF, showing (A) agreement between [18F]F-flotufolastat -derived SRF and [99mTc]Tc-MAG3-derived SRF, and (B) agreement between [68Ga]Ga-PSMA-11-derived SRF and [99mTc]Tc-MAG3-derived SRF Solid blue lines represent mean differences, while dashed brown lines indicate the limits of agreement (± 1.96 SD) 18F = Fluorine-18; 68Ga = Gallium-68; MAG3 = mercapto-acetyltriglycine; PET = positron emission tomography; SD = standard deviation; SRF = split renal function; ⁹⁹ᵐTc = Technetium-99 m
Fig. 3
Fig. 3
Correlation between [68Ga]Ga-PSMA-11-based SRF and [99mTc]Tc-MAG3-derived SRF for the right kidney 68Ga = Gallium-68; MAG3 = mercapto-acetyltriglycine; PET = positron emission tomography; SRF = split renal function; ⁹⁹ᵐTc = Technetium-99 m
Fig. 4
Fig. 4
Correlation between [18F]F-flotufolastat-based SRF and [99mTc]Tc-MAG3-derived SRF for the right kidney 18F = Fluorine-18; MAG3 = mercapto-acetyltriglycine; PET = positron emission tomography; SRF = split renal function; ⁹⁹ᵐTc = Technetium-99 m
Fig. 5
Fig. 5
ROC curves for (A) [18F]F-flotufolastat PSMA-PET-derived SRF in identifying [99mTc]Tc-MAG3-SRF < 25%; (B) [18F]F-flotufolastat-derived SRF in identifying [99mTc]Tc-MAG3-SRF < 40%; (C) [68Ga]Ga-PSMA-11-derived SRF in identifying [99mTc]Tc-MAG3-SRF < 25%; and (D) [68Ga]Ga-PSMA-11-PSMA-PET-derived SRF in identifying [99mTc]Tc-MAG3-SRF < 40% 18F = Fluorine-18; 68Ga = Gallium-68; AUC = area under the ROC curve; MAG3 = mercapto-acetyltriglycine; PET = positron emission tomography; PSMA = prostate-specific membrane antigen; ROC = receiver operating characteristic; SRF = split renal function; ⁹⁹ᵐTc = Technetium-99 m
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References

    1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. - PubMed
    1. Chodyla MK, Eiber M, Wetter A, Rauscher I. [Hybrid imaging in prostate cancer : Status quo and future applications]. Radiologe. 2020;60:386–93. - DOI - PubMed
    1. Park SY, Zacharias C, Harrison C, et al. Gallium 68 PSMA-11 PET/MR imaging in patients with intermediate- or high-risk prostate cancer. Radiology. 2018;288:495–505. - DOI - PubMed
    1. Ferraro DA, Muehlematter UJ, Garcia Schuler HI, et al. (68)Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer. Eur J Nucl Med Mol Imaging. 2020;47:147–59. - DOI - PubMed
    1. Afshar-Oromieh A, Avtzi E, Giesel FL, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209. - DOI - PMC - PubMed

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