A safe and inexpensive method for setting up the Westergren ESR.

Abstract

<b>385</b> <h3><b>Objectives</b></h3> Organic cation transporters (OCTs) are members of the solute carrier 22 family of transporter proteins that are involved in absorption, distribution, and excretion of organic cations. OCTs are expressed in the kidney, liver, intestine, and other organs, transporting organic cationic compounds. Metformin is a widely used drug which is a substrate for specific OCTs. We have successfully generated 11C-metformin and the aim of this study was to characterize its pharmacokinetic properties. <h3><b>Methods</b></h3> Three strategies were used to validate 11C-metformin. 1) Uptake of 11C-metformin was studied in-vitro in the kidney proximal tubule cell line LLC-PK1 in the presence of increasing doses of metformin. 2) Anaesthetised male Sprague-Dawley rats (250-300 g) were scanned (Concorde R4 microPET) for 90 min after iv injection of 8-25 MBq 11C-metformin at baseline, and after administration of metformin (50 mg/kg) and various OCT inhibitors (OCTI). 3) Female Landrace pigs (40 kg) placed in a Siemens Biograph TruePoint 64 PET/CT were scanned for 120 min after iv injection of 250 MBq 11C-metformin at baseline and after treatment with metformin (1.5 g) and various OCTI. <h3><b>Results</b></h3> 1) Uptake of 11C-metformin in LLC-PK1 cells was rapid and inhibited in a dose dependent manner by metformin. 2) Rat microPET images showed 11C-metformin uptake in liver and kidney, the kinetics of which was changed after challenging animals with OCTI. 3) In pigs, 80% of injected metformin dose was rapidly present in the kidney and OCTI caused a delayed renal uptake and clearance compared to baseline, and liver kinetics was likewise changed. <h3><b>Conclusions</b></h3> 11C-Metformin PET/CT may prove to be useful in humans for characterization and quantification of renal and liver function and expression of OCTs during physiological conditions and in patients with kidney or liver diseases.