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Radiosynthesis of novel pitavastatin derivative ([ 18 F]PTV‐F1) as a tracer for hepatic OATP using a one‐pot synthetic procedure
Author(s) -
Kimura Hiroyuki,
Yagi Yusuke,
Arimitsu Kenji,
Maeda Kazuya,
Ikejiri Kazuaki,
Takano Junichi,
Kusuhara Hiroyuki,
Kagawa Shinya,
Ono Masahiro,
Sugiyama Yuichi,
Saji Hideo
Publication year - 2016
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3464
Subject(s) - pitavastatin , radiosynthesis , chemistry , organic anion transporting polypeptide , radiochemistry , yield (engineering) , derivative (finance) , pharmacokinetics , positron emission tomography , pharmacology , biochemistry , nuclear medicine , transporter , statin , medicine , materials science , gene , economics , financial economics , metallurgy
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.