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Pedersen L, Jensen JB, Wogensen L, et al. Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease. EJNMMI Res. 2016;6(1):54doi: 10.1186/s13550-016-0211-x.
Pedersen, L., Jensen, J. B., Wogensen, L., Munk, O. L., Jessen, N., Frøkiær, J., & Jakobsen, S. (2016). Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease. EJNMMI research, 6(1), 54. https://doi.org/10.1186/s13550-016-0211-x
Pedersen, Lea, et al. "Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease." EJNMMI research vol. 6,1 (2016): 54. doi: https://doi.org/10.1186/s13550-016-0211-x
Pedersen L, Jensen JB, Wogensen L, Munk OL, Jessen N, Frøkiær J, Jakobsen S. Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease. EJNMMI Res. 2016 Dec;6(1):54. doi: 10.1186/s13550-016-0211-x. Epub 2016 Jun 23. PMID: 27339044; PMCID: PMC4919269.
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EJNMMI Res. 2016 Dec;6(1):54. doi: 10.1186/s13550-016-0211-x. Epub 2016 Jun 23.

Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease.

EJNMMI research

Lea Pedersen, Jonas Brorson Jensen, Lise Wogensen, Ole Lajord Munk, Niels Jessen, Jørgen Frøkiær, Steen Jakobsen

Affiliations

  1. Research Laboratory for Biochemical Pathology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  2. Department of Nuclear Medicine & PET Center, Aarhus University Hospital, DK-8000, Aarhus C, Denmark.
  3. Department of Nuclear Medicine & PET Center, Aarhus University Hospital, DK-8000, Aarhus C, Denmark. [email protected].

PMID: 27339044 PMCID: PMC4919269 DOI: 10.1186/s13550-016-0211-x

Abstract

BACKGROUND: Organic cation transporters (OCTs) in the renal proximal tubule are important for the excretion of both exo- and endogenous compounds, and chronic kidney disease (CKD) alter the expression of OCT. Metformin is a well-known substrate for OCT, and recently, we demonstrated that positron emission tomography (PET) with 11C-labelled metformin ((11)C-metformin) is a promising approach to evaluate the function of OCT. The aim of this study is therefore to examine renal pharmacokinetics of (11)C-metformin and expression of OCTs in a transgenic (RenTGF-β1) mouse model of CKD.

METHODS: Age- and sex-matched RenTGF-β1 (Tg) and wildtype (WT) mice were used (5-8/group). Animals received an iv bolus of (11)C-metformin followed by 90-min dynamic PET and MRI scan. PET data were analysed using a one-tissue compartment model. Renal protein abundance of OCT2 (by Western blot) as well as OCT1, OCT2, and MATE1 messenger RNA (mRNA) (by RT-PCR) was examined.

RESULTS: Protein expression of the basolateral uptake transporter OCT2 was 1.5-fold lower in Tg mice compared to WT mice while OCT1 and MATE1 mRNA expression did not differ between the two groups. The influx rate constant of (11)C-metformin in renal cortex (K 1) was 2.2-fold lower in transgenic mice whereas the backflux rate constant (k 2) was similar in the two groups, consistent with protein expression. Total body clearance (TBC) correlated within each group linearly with K 1.

CONCLUSIONS: In conclusion, this study demonstrates that both renal OCT2 expression and (11)C-metformin uptake are reduced in CKD mice. This potentially makes (11)C-metformin valuable as a PET probe to evaluate kidney function.

Keywords: 11C-metformin; Chronic kidney disease; Mouse model; PET

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