Biological Distribution of Orally Administered [<sup>123</sup>I]MIBG for Estimating Gastrointestinal Tract Absorption

Gastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [<sup>123</sup>I]MIBG administration. [<sup>123</sup>I]MIBG was added to cultures of human embryonic kidney (HEK)293 cells expressing human organ...

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Main Authors: Masato Kobayashi, Asuka Mizutani, Yuka Muranaka, Kodai Nishi, Hisakazu Komori, Ryuichi Nishii, Naoto Shikano, Takeo Nakanishi, Ikumi Tamai, Keiichi Kawai
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/1/61
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author Masato Kobayashi
Asuka Mizutani
Yuka Muranaka
Kodai Nishi
Hisakazu Komori
Ryuichi Nishii
Naoto Shikano
Takeo Nakanishi
Ikumi Tamai
Keiichi Kawai
author_facet Masato Kobayashi
Asuka Mizutani
Yuka Muranaka
Kodai Nishi
Hisakazu Komori
Ryuichi Nishii
Naoto Shikano
Takeo Nakanishi
Ikumi Tamai
Keiichi Kawai
author_sort Masato Kobayashi
collection DOAJ
description Gastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [<sup>123</sup>I]MIBG administration. [<sup>123</sup>I]MIBG was added to cultures of human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)2B1, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)1, OCT2, and OCT3 with and without cimetidine (an OCTN and OCT inhibitor) and L-carnitine (an OCTN inhibitor). Biodistribution analyses and single-photon emission computed tomography (SPECT) imaging in normal and dextran sodium sulfate (DSS)-induced experimental colitis mice were conducted using [<sup>123</sup>I]MIBG with and without cimetidine. [<sup>123</sup>I]MIBG uptake was significantly higher in HEK293/OCTN1, 2, and OCT1-3 cells than in mock cells. Uptake via OCTN was inhibited by L-carnitine, whereas OCT-mediated uptake was inhibited by cimetidine. Biodistribution analyses and SPECT imaging studies showed significantly lower accumulation of [<sup>123</sup>I]MIBG in the blood, heart, liver, and bladder in DSS-induced experimental colitis mice and mice with cimetidine loading compared with normal mice, whereas significantly higher accumulation in the stomach and kidney was observed after [<sup>123</sup>I]MIBG injection. [<sup>123</sup>I]MIBG imaging after oral administration can be used to estimate gastrointestinal absorption in the small intestine via OCTN and/or OCT by measuring radioactivity in the heart, liver, and bladder.
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spelling doaj.art-bae6afbbab2244dab82add208d3d30cd2023-11-23T15:03:14ZengMDPI AGPharmaceutics1999-49232021-12-011416110.3390/pharmaceutics14010061Biological Distribution of Orally Administered [<sup>123</sup>I]MIBG for Estimating Gastrointestinal Tract AbsorptionMasato Kobayashi0Asuka Mizutani1Yuka Muranaka2Kodai Nishi3Hisakazu Komori4Ryuichi Nishii5Naoto Shikano6Takeo Nakanishi7Ikumi Tamai8Keiichi Kawai9Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanFaculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanFaculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanDepartment of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanFaculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, JapanDepartment of Molecular Imaging and Theranostics, Institute for Quantum Medical Science Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage, Chiba 263-8555, JapanDepartment of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Inashiki, Ibaraki 300-0394, JapanFaculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, JapanFaculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, JapanFaculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanGastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [<sup>123</sup>I]MIBG administration. [<sup>123</sup>I]MIBG was added to cultures of human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)2B1, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)1, OCT2, and OCT3 with and without cimetidine (an OCTN and OCT inhibitor) and L-carnitine (an OCTN inhibitor). Biodistribution analyses and single-photon emission computed tomography (SPECT) imaging in normal and dextran sodium sulfate (DSS)-induced experimental colitis mice were conducted using [<sup>123</sup>I]MIBG with and without cimetidine. [<sup>123</sup>I]MIBG uptake was significantly higher in HEK293/OCTN1, 2, and OCT1-3 cells than in mock cells. Uptake via OCTN was inhibited by L-carnitine, whereas OCT-mediated uptake was inhibited by cimetidine. Biodistribution analyses and SPECT imaging studies showed significantly lower accumulation of [<sup>123</sup>I]MIBG in the blood, heart, liver, and bladder in DSS-induced experimental colitis mice and mice with cimetidine loading compared with normal mice, whereas significantly higher accumulation in the stomach and kidney was observed after [<sup>123</sup>I]MIBG injection. [<sup>123</sup>I]MIBG imaging after oral administration can be used to estimate gastrointestinal absorption in the small intestine via OCTN and/or OCT by measuring radioactivity in the heart, liver, and bladder.https://www.mdpi.com/1999-4923/14/1/61[<sup>123</sup>I]MIBGSPECTimagingdrug transportersgastrointestinal tract absorption
spellingShingle Masato Kobayashi
Asuka Mizutani
Yuka Muranaka
Kodai Nishi
Hisakazu Komori
Ryuichi Nishii
Naoto Shikano
Takeo Nakanishi
Ikumi Tamai
Keiichi Kawai
Biological Distribution of Orally Administered [<sup>123</sup>I]MIBG for Estimating Gastrointestinal Tract Absorption
Pharmaceutics
[<sup>123</sup>I]MIBG
SPECT
imaging
drug transporters
gastrointestinal tract absorption
title Biological Distribution of Orally Administered [<sup>123</sup>I]MIBG for Estimating Gastrointestinal Tract Absorption
title_full Biological Distribution of Orally Administered [<sup>123</sup>I]MIBG for Estimating Gastrointestinal Tract Absorption
title_fullStr Biological Distribution of Orally Administered [<sup>123</sup>I]MIBG for Estimating Gastrointestinal Tract Absorption
title_full_unstemmed Biological Distribution of Orally Administered [<sup>123</sup>I]MIBG for Estimating Gastrointestinal Tract Absorption
title_short Biological Distribution of Orally Administered [<sup>123</sup>I]MIBG for Estimating Gastrointestinal Tract Absorption
title_sort biological distribution of orally administered sup 123 sup i mibg for estimating gastrointestinal tract absorption
topic [<sup>123</sup>I]MIBG
SPECT
imaging
drug transporters
gastrointestinal tract absorption
url https://www.mdpi.com/1999-4923/14/1/61
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