title: Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease.
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.
authors.affiliation: Research Laboratory for Biochemical Pathology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Lea
authors.initials: L
authors.lastname: Pedersen
authors.affiliation: Research Laboratory for Biochemical Pathology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Nuclear Medicine & PET Center, Aarhus University Hospital, DK-8000, Aarhus C, Denmark.
authors.forename: Jonas Brorson
authors.initials: JB
authors.lastname: Jensen
authors.affiliation: Research Laboratory for Biochemical Pathology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Wogensen
authors.affiliation: Department of Nuclear Medicine & PET Center, Aarhus University Hospital, DK-8000, Aarhus C, Denmark.
authors.forename: Ole Lajord
authors.initials: OL
authors.lastname: Munk
authors.affiliation: Research Laboratory for Biochemical Pathology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.affiliation: Department of Nuclear Medicine & PET Center, Aarhus University Hospital, DK-8000, Aarhus C, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiær
authors.affiliation: Department of Nuclear Medicine & PET Center, Aarhus University Hospital, DK-8000, Aarhus C, Denmark. jakobsen.steen@gmail.com.
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
keywords: 11C-metformin; Chronic kidney disease; Mouse model; PET