Published in:
Open Access 01-12-2016 | Original research
Renal PET-imaging with 11C-metformin in a transgenic mouse model for chronic kidney disease
Published in: EJNMMI Research | Issue 1/2016
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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 (11C-metformin) is a promising approach to evaluate the function of OCT. The aim of this study is therefore to examine renal pharmacokinetics of 11C-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 11C-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 11C-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 11C-metformin uptake are reduced in CKD mice. This potentially makes 11C-metformin valuable as a PET probe to evaluate kidney function.