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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 06-01-2022 | Chronic Kidney Disease | Original Article

[⁶⁸ Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease

Authors: Patrick Conen, Francesca Pennetta, Katharina Dendl, Fabian Hertel, Andreas Vogg, Uwe Haberkorn, Frederik L. Giesel, Felix M. Mottaghy

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2022

Abstract

Purpose

Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake.

Methods

In 81 patients receiving either one of the following molecular imaging probes, [⁶⁸ Ga]Ga-FAPI, [⁶⁸ Ga]Ga-PSMA, or [⁶⁸ Ga]Ga-DOTATOC, kidney function parameters were correlated with SUVmax and SUVmean of the renal parenchyma and background activity measured in lung parenchyma, myocardium, gluteal muscle, and the abdominal aorta. Patients were clustered according to their grade of chronic kidney disease (CKD), and a regression analysis and one-way ANOVA were conducted in this retrospective analysis.

Results

We found a negative correlation between GFR and [⁶⁸ Ga]Ga-FAPI uptake for both SUVmax and SUVmean values, whereas background activity showed no correlation with GFR. [⁶⁸ Ga]Ga-DOTATOC and [⁶⁸ Ga]Ga-PSMA did not correlate between CKD stage and intra-renal parenchymal radiotracer uptake. Only [⁶⁸ Ga]Ga-PSMA background activity exhibited a positive correlation with GFR suggesting an unspecific binding/retention potentially due to longer circulation times.

Conclusion

There is a significant negative correlation between renal parenchymal [⁶⁸ Ga]Ga-FAPI uptake and GFR, which was not the case for [⁶⁸ Ga]Ga-DOTATOC and [⁶⁸ Ga]Ga-PSMA. This correlation suggests a specific binding of FAPI rather than a potential unspecific retention in the renal parenchyma, underlining the potential value of [⁶⁸ Ga]Ga-FAPI for the noninvasive quantitative evaluation of kidney fibrosis.

Stevens PE, Levin A. Kidney disease: improving global outcomes chronic kidney disease guideline development work group M. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline Ann Intern Med. 2013 158 825 30 10.7326/0003-4819-158-11-201306040-00007

Jiang K, Ferguson CM, Lerman LO. Noninvasive assessment of renal fibrosis by magnetic resonance imaging and ultrasound techniques. Transl Res. 2019;209:105–20. https://doi.org/10.1016/j.trsl.2019.02.009.CrossRefPubMedPubMedCentral

Sun Q, Baues M, Klinkhammer BM, Ehling J, Djudjaj S, Drude NI, et al. Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis. Science translational medicine. 2019;11. doi:https://doi.org/10.1126/scitranslmed.aat4865.

Baues M, Klinkhammer BM, Ehling J, Gremse F, van Zandvoort M, Reutelingsperger CPM, et al. A collagen-binding protein enables molecular imaging of kidney fibrosis in vivo. Kidney Int. 2020;97:609–14. https://doi.org/10.1016/j.kint.2019.08.029.CrossRefPubMed

Poggio ED. Imaging as a noninvasive tool for evaluating interstitial fibrosis in kidney allografts. Clin J Am Soc Nephrol. 2019;14:1286–7. https://doi.org/10.2215/cjn.08520719.CrossRefPubMedPubMedCentral

Hanssen O, Lovinfosse P, Weekers L, Hustinx R, Jouret F. (18)F-FDG positron emission tomography in non-oncological renal pathology: current indications and perspectives. Nephrol Ther. 2019;15:430–8. https://doi.org/10.1016/j.nephro.2018.11.007.CrossRefPubMed

Klinkhammer BM, Lammers T, Mottaghy FM, Kiessling F, Floege J, Boor P. Non-invasive molecular imaging of kidney diseases. Nat Rev Nephrol. 2021. https://doi.org/10.1038/s41581-021-00440-4.CrossRefPubMedPubMedCentral

Zhou Y, Yang X, Liu H, Luo W, Liu H, Lv T, et al. Value of [(68)Ga]Ga-FAPI-04 imaging in the diagnosis of renal fibrosis. Eur J Nucl Med Mol Imaging. 2021. https://doi.org/10.1007/s00259-021-05343-x.CrossRefPubMedPubMedCentral

Meran S, Steadman R. Fibroblasts and myofibroblasts in renal fibrosis. Int J Exp Pathol. 2011;92:158–67. https://doi.org/10.1111/j.1365-2613.2011.00764.x.CrossRefPubMedPubMedCentral

10.

Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60:801–5.CrossRef

11.

Wang XM, Yao T-W, Nadvi NA, Osborne B, McCaughan GW, Gorrell MD. Fibroblast activation protein and chronic liver disease. Front Biosci. 2008;13:80.

12.

Bozkurt MF, Virgolini I, Balogova S, Beheshti M, Rubello D, Decristoforo C, et al. Guideline for PET/CT imaging of neuroendocrine neoplasms with (68)Ga-DOTA-conjugated somatostatin receptor targeting peptides and (18)F-DOPA. Eur J Nucl Med Mol Imaging. 2017;44:1588–601. https://doi.org/10.1007/s00259-017-3728-y.CrossRefPubMed

13.

Bhandari S, Watson N, Long E, Sharpe S, Zhong W, Xu SZ, et al. Expression of somatostatin and somatostatin receptor subtypes 1–5 in human normal and diseased kidney. J Histochem Cytochem. 2008;56:733–43. https://doi.org/10.1369/jhc.2008.950998.CrossRefPubMedPubMedCentral

14.

Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;91:528–39. https://doi.org/10.1002/jcb.10661.CrossRefPubMed

15.

Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. (68)Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017;44:1014–24. doi:https://doi.org/10.1007/s00259-017-3670-z.

16.

Chang SS. Overview of prostate-specific membrane antigen. Rev Urol. 2004;6(Suppl 10):S13–8.PubMedPubMedCentral

17.

Lindner T, Loktev A, Altmann A, Giesel F, Kratochwil C, Debus J, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;59:1415–22. https://doi.org/10.2967/jnumed.118.210443.CrossRef

18.

Meyer C, Dahlbom M, Lindner T, Vauclin S, Mona C, Slavik R, et al. Radiation dosimetry and biodistribution of (68)Ga-FAPI-46 PET imaging in cancer patients. J Nucl Med. 2020;61:1171–7. https://doi.org/10.2967/jnumed.119.236786.CrossRefPubMedPubMedCentral

19.

Behrendt FF, Temur Y, Verburg FA, Palmowski M, Krohn T, Pietsch H, et al. PET/CT in lung cancer: Influence of contrast medium on quantitative and clinical assessment. Eur Radiol. 2012;22:2458–64. https://doi.org/10.1007/s00330-012-2515-1.CrossRefPubMed

20.

Eder M, Schäfer M, Bauder-Wüst U, Hull WE, Wängler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23:688–97. https://doi.org/10.1021/bc200279b.CrossRefPubMed

21.

Martin R, Juttler S, Muller M, Wester HJ. Cationic eluate pretreatment for automated synthesis of [(6)(8)Ga]CPCR4.2. Nucl Med Biol. 2014;41:84–9. doi:https://doi.org/10.1016/j.nucmedbio.2013.09.002.

22.

Sandström M, Velikyan I, Garske-Román U, Sörensen J, Eriksson B, Granberg D, et al. Comparative biodistribution and radiation dosimetry of 68Ga-DOTATOC and 68Ga-DOTATATE in patients with neuroendocrine tumors. J Nucl Med. 2013;54:1755–9. https://doi.org/10.2967/jnumed.113.120600.CrossRefPubMed

23.

Benešová M, Schäfer M, Bauder-Wüst U, Afshar-Oromieh A, Kratochwil C, Mier W, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med. 2015;56:914–20. https://doi.org/10.2967/jnumed.114.147413.CrossRefPubMed

24.

Giesel FL, Kratochwil C, Lindner T, Marschalek MM, Loktev A, Lehnert W, et al. (68)Ga-FAPI PET/CT: biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers. J Nucl Med. 2019;60:386–92. https://doi.org/10.2967/jnumed.118.215913.CrossRefPubMedPubMedCentral

25.

Nakhoul N, Batuman V. Role of proximal tubules in the pathogenesis of kidney disease. Contrib Nephrol. 2011;169:37–50. https://doi.org/10.1159/000313944.CrossRefPubMed

26.

Filss C, Heinzel A, Miiller B, Vogg ATJ, Langen KJ, Mottaghy FM. Relevant tumor sink effect in prostate cancer patients receiving 177Lu-PSMA-617 radioligand therapy. Nuklearmedizin. 2018;57:19–25. https://doi.org/10.3413/Nukmed-0937-17-10.CrossRefPubMed

Title: [68 Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease
Authors: Patrick Conen
Francesca Pennetta
Katharina Dendl
Fabian Hertel
Andreas Vogg
Uwe Haberkorn
Frederik L. Giesel
Felix M. Mottaghy
Publication date: 06-01-2022
Publisher: Springer Berlin Heidelberg
Keyword: Chronic Kidney Disease
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-021-05660-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

[⁶⁸ Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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