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      First experiences with dynamic renal [ 68Ga]Ga-DOTA PET/CT: a comparison to renal scintigraphy and compartmental modelling to non-invasively estimate the glomerular filtration rate

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          Abstract

          Purpose

          The determination of the glomerular filtration rate (GFR) is decisive for a variety of clinical issues, for example, to monitor the renal function in radionuclide therapy patients. Renal scintigraphy using glomerularly filtered tracers allows combined acquisition of renograms and GFR estimation but requires repeated blood sampling for several hours. In contrast, dynamic PET imaging using the glomerularly filtered tracer [ 68Ga]Ga-DOTA bears the potential to non-invasively estimate the GFR by compartmental kinetic modelling. Here, we report the, to our knowledge, first comparison of human renal dynamic [ 68Ga]Ga-DOTA PET imaging in comparison to renal scintigraphy and compare PET-derived to serum creatinine-derived GFR measurements.

          Methods

          Dynamic [ 68Ga]Ga-DOTA PET data were acquired for 30 min immediately after tracer injection in 12 patients. PET and renal scintigraphy images were visually interpreted in a consensus read by three nuclear medicine physicians. The functional renal cortex was segmented to obtain time-activity curves. The arterial input function was estimated from the PET signal in the abdominal aorta. Single-compartmental tracer kinetic modelling was performed to calculate the GFR using complete 30-min (GFR PET-30) and reduced 15-min PET data sets (GFR PET-15) to evaluate whether a shorter acquisition time is sufficient for an accurate GFR estimation. A modified approach excluding minutes 2 to 10 was applied to reduce urinary spill-over effects. Serum creatinine-derived GFR CKD (CKD-EPI-formula) was used as reference standard.

          Results

          PET image interpretation revealed the same findings as conventional scintigraphy (2/12 patients with both- and 1/12 patients with right-sided urinary obstruction). Model fit functions were substantially improved for the modified approach to exclude spill-over. Depending on the modelling approach, GFR CKD and both GFR PET-30 and GFR PET-15 were well correlated with interclass correlation coefficients (ICCs) from 0.74 to 0.80 and Pearson’s correlation coefficients (PCCs) from 0.74 to 0.81. For a subgroup of patients with undisturbed urinary efflux ( n = 9), correlations were good to excellent (ICCs from 0.82 to 0.95 and PCCs from 0.83 to 0.95). Overall, GFR PET-30 and GFR PET-15 were excellently correlated (ICCs from 0.96 to 0.99 and PCCs from 0.96 to 0.99).

          Conclusion

          Renal [ 68Ga]Ga-DOTA PET can be a suitable alternative to conventional scintigraphy. Visual assessment of PET images and conventional renograms revealed comparable results. GFR values derived by non-invasive single-compartmental-modelling of PET data show a good correlation to serum creatinine-derived GFR values. In patients with undisturbed urinary efflux, the correlation was excellent. Dynamic PET data acquisition for 15 min is sufficient for visual evaluation and GFR derivation.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00259-022-05781-1.

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          Most cited references31

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          A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research.

          Intraclass correlation coefficient (ICC) is a widely used reliability index in test-retest, intrarater, and interrater reliability analyses. This article introduces the basic concept of ICC in the content of reliability analysis.
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            A new equation to estimate glomerular filtration rate.

            Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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              STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT

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                Author and article information

                Contributors
                david.kersting@uni-due.de
                Journal
                Eur J Nucl Med Mol Imaging
                Eur J Nucl Med Mol Imaging
                European Journal of Nuclear Medicine and Molecular Imaging
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1619-7070
                1619-7089
                12 April 2022
                12 April 2022
                : 1-14
                Affiliations
                [1 ]GRID grid.410718.b, ISNI 0000 0001 0262 7331, Department of Nuclear Medicine, , University Hospital Essen, West German Cancer Center (WTZ), University of Duisburg-Essen, ; Hufelandstrasse 55, 45147 Essen, Germany
                [2 ]German Cancer Consortium (DKTK, Partner Site Essen/Düsseldorf), Essen, Germany
                [3 ]GRID grid.16149.3b, ISNI 0000 0004 0551 4246, Department of Nuclear Medicine, , University Hospital Muenster, University of Muenster, ; Muenster, Germany
                [4 ]GRID grid.410718.b, ISNI 0000 0001 0262 7331, Department of Diagnostic and Interventional Radiology and Neuroradiology, , University Hospital Essen, University of Duisburg-Essen, ; Essen, Germany
                Author information
                http://orcid.org/0000-0002-8451-1830
                Article
                5781
                10.1007/s00259-022-05781-1
                9002049
                35412053
                e5dc6165-4005-45d9-859b-f0cee7d03b50
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 February 2022
                : 26 March 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: FU356/12-1
                Award Recipient :
                Funded by: Universitätsklinikum Essen (8912)
                Categories
                Original Article

                Radiology & Imaging
                dota pet,renal pet/ct,glomerular filtration rate,compartmental kinetic modelling,dynamic pet

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