Abstract
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Objectives The liver plays an important role in the excretion of xenobiotics, including many kinds of drugs, and various transporters and metabolizing enzymes are involved in the process. Organic anion transporting peptide (OATP) is known as involved in hepatic uptake. Since OATP leads to variation of the drug effect, it is important to evaluate the OATP function for prediction of therapeutic efficacy. In this study, we synthesized [18F]Pitavastatin ([18F]PTV) and investigated its potential as a PET probe to evaluate hepatic transport quantitatively.
Methods [18F]PTV was synthesized from a boronic ester precursor with 4-[18F]Fluoroiodobenzene ([18F]FIB) using suzuki-coupling reaction under microwave heating. Metabolite analysis in blood, bile and liver was carried out in SD rat using TLC and autoradiography. Biodistribution study and In vivo PET/CT scan was performed for the evaluation of liver uptake in SD rat.
Results Suzuki-coupling reaction with [18F]FIB gave [18F]PTV in 30% RCY and >99% RCP. [18F]PTV remained intact in the liver 40 min p.i. (>95% intact). In biodistribution study, [18F]PTV mainly distributed in the liver in the early stage and gradually into the intestine, which suggests that a part of the administrated [18F]PTV was excreted in the bile. Administration of the OATP inhibitor rifampicin significantly reduced uptake of radioactivity in the liver. Furthermore, PET studies with [18F]PTV agreed with the biodistribution data, demonstrating that radioactivity was predominately taken by the liver and the peak concentration was observed at 10 min p.i. and CLuptakeliver derived from integration plot method was 9.65 ± 1.07 mL/min/kg.
Conclusions [18F]PTV have the potential to be a PET probe for evaluation of OATP function in the liver.