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Inhibition of the Hepatic Uptake of (99m)Tc-Tetrofosmin Using an Organic Cation Transporter Blocker

The accumulation of high levels of (99m)Tc-tetrofosmin ((99m)Tc-TF) in the hepatobiliary system can lead to imaging artifacts and interference with diagnosis. The present study investigated the transport mechanisms of (99m)Tc-TF and attempted to apply competitive inhibition using a specific inhibito...

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Autores principales: Nishi, Kodai, Kobayashi, Masato, Kikuchi, Minori, Mizutani, Asuka, Muranaka, Yuka, Tamai, Ikumi, Kawai, Keiichi, Kudo, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309083/
https://www.ncbi.nlm.nih.gov/pubmed/34371764
http://dx.doi.org/10.3390/pharmaceutics13071073
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author Nishi, Kodai
Kobayashi, Masato
Kikuchi, Minori
Mizutani, Asuka
Muranaka, Yuka
Tamai, Ikumi
Kawai, Keiichi
Kudo, Takashi
author_facet Nishi, Kodai
Kobayashi, Masato
Kikuchi, Minori
Mizutani, Asuka
Muranaka, Yuka
Tamai, Ikumi
Kawai, Keiichi
Kudo, Takashi
author_sort Nishi, Kodai
collection PubMed
description The accumulation of high levels of (99m)Tc-tetrofosmin ((99m)Tc-TF) in the hepatobiliary system can lead to imaging artifacts and interference with diagnosis. The present study investigated the transport mechanisms of (99m)Tc-TF and attempted to apply competitive inhibition using a specific inhibitor to reduce (99m)Tc-TF hepatic accumulation. In this in vitro study, (99m)Tc-TF was incubated in HEK293 cells expressing human organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, organic anion transporter 2 (OAT2), organic cation transporter 1 (OCT1), OCT2, and Na(+)-taurocholate cotransporting polypeptide with or without each specific inhibitor to evaluate the contribution of each transporter to (99m)Tc-TF transportation. In vivo studies, dynamic planar imaging, and single photon emission computed tomography (SPECT) experiments with rats were performed to observe alterations to (99m)Tc-TF pharmacokinetics using cimetidine (CMT) as an OCT1 inhibitor. Time–activity curves in the liver and heart were acquired from dynamic data, and the (99m)Tc-TF uptake ratio was calculated from SPECT. From the in vitro study, (99m)Tc-TF was found to be transported by OCT1 and OCT2. When CMT-preloaded rats and control rats were compared, the hepatic accumulation of the (99m)Tc-TF was reduced, and the time to peak heart count shifted to an earlier stage. The hepatic accumulation of (99m)Tc-TF was markedly suppressed, and the heart-to-liver ratio increased 1.6-fold. The pharmacokinetics of (99m)Tc-TF were greatly changed by OCT1 inhibitor. Even in humans, the administration of OCT1 inhibitor before cardiac SPECT examination may reduce (99m)Tc-TF hepatic accumulation and contribute to the suppression of artifacts and the improvement of SPECT image quality.
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spelling pubmed-83090832021-07-25 Inhibition of the Hepatic Uptake of (99m)Tc-Tetrofosmin Using an Organic Cation Transporter Blocker Nishi, Kodai Kobayashi, Masato Kikuchi, Minori Mizutani, Asuka Muranaka, Yuka Tamai, Ikumi Kawai, Keiichi Kudo, Takashi Pharmaceutics Article The accumulation of high levels of (99m)Tc-tetrofosmin ((99m)Tc-TF) in the hepatobiliary system can lead to imaging artifacts and interference with diagnosis. The present study investigated the transport mechanisms of (99m)Tc-TF and attempted to apply competitive inhibition using a specific inhibitor to reduce (99m)Tc-TF hepatic accumulation. In this in vitro study, (99m)Tc-TF was incubated in HEK293 cells expressing human organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, organic anion transporter 2 (OAT2), organic cation transporter 1 (OCT1), OCT2, and Na(+)-taurocholate cotransporting polypeptide with or without each specific inhibitor to evaluate the contribution of each transporter to (99m)Tc-TF transportation. In vivo studies, dynamic planar imaging, and single photon emission computed tomography (SPECT) experiments with rats were performed to observe alterations to (99m)Tc-TF pharmacokinetics using cimetidine (CMT) as an OCT1 inhibitor. Time–activity curves in the liver and heart were acquired from dynamic data, and the (99m)Tc-TF uptake ratio was calculated from SPECT. From the in vitro study, (99m)Tc-TF was found to be transported by OCT1 and OCT2. When CMT-preloaded rats and control rats were compared, the hepatic accumulation of the (99m)Tc-TF was reduced, and the time to peak heart count shifted to an earlier stage. The hepatic accumulation of (99m)Tc-TF was markedly suppressed, and the heart-to-liver ratio increased 1.6-fold. The pharmacokinetics of (99m)Tc-TF were greatly changed by OCT1 inhibitor. Even in humans, the administration of OCT1 inhibitor before cardiac SPECT examination may reduce (99m)Tc-TF hepatic accumulation and contribute to the suppression of artifacts and the improvement of SPECT image quality. MDPI 2021-07-13 /pmc/articles/PMC8309083/ /pubmed/34371764 http://dx.doi.org/10.3390/pharmaceutics13071073 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nishi, Kodai
Kobayashi, Masato
Kikuchi, Minori
Mizutani, Asuka
Muranaka, Yuka
Tamai, Ikumi
Kawai, Keiichi
Kudo, Takashi
Inhibition of the Hepatic Uptake of (99m)Tc-Tetrofosmin Using an Organic Cation Transporter Blocker
title Inhibition of the Hepatic Uptake of (99m)Tc-Tetrofosmin Using an Organic Cation Transporter Blocker
title_full Inhibition of the Hepatic Uptake of (99m)Tc-Tetrofosmin Using an Organic Cation Transporter Blocker
title_fullStr Inhibition of the Hepatic Uptake of (99m)Tc-Tetrofosmin Using an Organic Cation Transporter Blocker
title_full_unstemmed Inhibition of the Hepatic Uptake of (99m)Tc-Tetrofosmin Using an Organic Cation Transporter Blocker
title_short Inhibition of the Hepatic Uptake of (99m)Tc-Tetrofosmin Using an Organic Cation Transporter Blocker
title_sort inhibition of the hepatic uptake of (99m)tc-tetrofosmin using an organic cation transporter blocker
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309083/
https://www.ncbi.nlm.nih.gov/pubmed/34371764
http://dx.doi.org/10.3390/pharmaceutics13071073
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