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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.

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