ArticleEJNMMI research2016
Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease.
Article in EJNMMI research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 5 citations in OpenAlex.
- Hepatic exposure of metformin in patients with non-alcoholic fatty liver disease.British journal of clinical pharmacology · 2019Trial
- Prediction of the Effects of Renal Impairment on Clearance for Organic Cation Drugs that Undergo Renal Secretion: A Simulation-Based Study.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
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7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundOrganic 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.
methodsAge- 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.
resultsProtein 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.
conclusionsIn 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.
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