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J Labelled Comp Radiopharm. 2016 Nov;59(13):565-575. doi: 10.1002/jlcr.3464. Epub 2016 Oct 2.

Radiosynthesis of novel pitavastatin derivative ([18 F]PTV-F1) as a tracer for hepatic OATP using a one-pot synthetic procedure.

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Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan.
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Shiga Medical Center Research Institute, Moriyama, Moriyama City, Shiga, Japan.
Sugiyama Laboratory, RIKEN Innovation Center, RIKEN Cluster for Industry Partnerships, RIKEN, Tsurumi-ku, Yokohama, Japan.


Pitavastatin is an antihyperlipidemic agent, a potent inhibitor of 3-hydroxymethyl-glutaryl-CoA reductase, which is selectively taken up into the liver mainly via hepatic organic anion transporting polypeptide 1B1 (OATP1B1). OATP1B1 can accept a variety of organic anions, and previous reports indicated that it is responsible for the hepatic clearance of several clinically used anionic drugs. Therefore, the pharmacokinetics and the hepatic distribution of pitavastatin provide an insight into the function of OATP1B1 in humans. For the development of the in vivo evaluation of OATP1B1 function by positron emission tomography imaging, we designed a novel [18 F]pitavastatin derivative ([18 F]PTV-F1), in which a [18 F]fluoroethoxy group is substituted for the [18 F]fluoro group of [18 F]pitavastatin, with the aim of convenient radiolabeling protocol and high radiochemical yield. In vitro studies suggested that transport activities of PTV-F1 mediated by OATP1B1 and OATP1B3 were very similar to those of pitavastatin and PTV-F1 was metabolically stable in human liver microsomes. In the radiosynthesis of [18 F]PTV-F1 from the tosylate precursor, nucleophilic fluorination and subsequent deprotection were performed using a one-pot procedure. [18 F]PTV-F1 was obtained with a radiochemical yield of 45% ± 3% (n = 3), and the operating time for the radiosynthesis of [18 F]PTV-F1 is very short (30 minutes) compared with [18 F]pitavastatin.


fluorine-18; one-pot radiosynthesis; pitavastatin derivatives; positron emission tomography

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