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Bioorg Med Chem. 2013 Dec 15;21(24):7584-90. doi: 10.1016/j.bmc.2013.10.041. Epub 2013 Nov 1.

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

Author information

1
RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: ewan_hume@riken.jp.

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.

KEYWORDS:

Hepatobiliary transport; Metformin; Multi-drug and toxin extrusion transporter 1 (MATE1); Positron emission tomography (PET); Pyrimethamine

PMID:
24238901
DOI:
10.1016/j.bmc.2013.10.041
[Indexed for MEDLINE]

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