The synthesis and biodistribution of [11C]metformin as a PET probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1) in vivo

Abstract In order to develop a new positron emission tomography (PET) probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1), 11 C-labelled metformin was synthesized and then evaluated as a PET probe. [ 11 C]Metformin ([ 11 C] 4 ) was synthesized in three steps, from [ 11 C]methyl iodide. Evaluation by small animal PET of [ 11 C] 4 showed that there was increased concentrations of [ 11 C] 4 in the livers of mice pre-treated with pyrimethamine, a potential inhibitor of MATEs, inhibiting the hepatobiliary excretion of metformin. Radiometabolite analysis showed that [ 11 C] 4 was not degraded in vivo during the PET scan. Biodistribution studies were undertaken and the organ distributions were extrapolated into a standard human model. In conclusion, [ 11 C] 4 may be useful as a PET probe to non-invasively study the in vivo function of hepatobiliary transport and drug–drug interactions, mediated by MATE1 in future clinical investigations.