Biological Distribution of Orally Administered [123I]MIBG for Estimating Gastrointestinal Tract Absorption

Masato Kobayashi; Asuka Mizutani; Yuka Muranaka; Kodai Nishi; Hisakazu Komori; Ryuichi Nishii; Naoto Shikano; Takeo Nakanishi; Ikumi Tamai; Keiichi Kawai

doi:10.3390/pharmaceutics14010061

Biological Distribution of Orally Administered [¹²³I]MIBG for Estimating Gastrointestinal Tract Absorption

Pharmaceutics. 2021 Dec 28;14(1):61. doi: 10.3390/pharmaceutics14010061.

Authors

Affiliations

¹ Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan.
² Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
³ Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.
⁴ Department 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, Japan.
⁵ Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Inashiki, Ibaraki 300-0394, Japan.
⁶ Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, Japan.
⁷ Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji, Fukui 910-1193, Japan.

Abstract

Gastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [¹²³I]MIBG administration. [¹²³I]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 [¹²³I]MIBG with and without cimetidine. [¹²³I]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 [¹²³I]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 [¹²³I]MIBG injection. [¹²³I]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.

Keywords: SPECT; [123I]MIBG; drug transporters; gastrointestinal tract absorption; imaging.

Abstract

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