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
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
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DOI：
10.1016/j.bmc.2013.10.041
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发表时间：
2013-12-15
影响因子：
3.5
通讯作者：
Watanabe, Yasuyoshi
中科院分区：
文献类型：
--
作者：
Hume, W. Ewan;Shingaki, Tomotaka;Watanabe, Yasuyoshi
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), C-11-labelled metformin was synthesized and then evaluated as a PET probe. [C-11] Metformin ([C-11]4) was synthesized in three steps, from [C-11] methyl iodide. Evaluation by small animal PET of [C-11]4 showed that there was increased concentrations of [C-11]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 [C-11]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, [C-11]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. (C) 2013 Elsevier Ltd. All rights reserved.
