Biological Distribution of Orally Administered [<sup>123</sup>I]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
Affiliations
Masato Kobayashi
Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Asuka Mizutani
Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Yuka Muranaka
Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Kodai Nishi
Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Hisakazu Komori
Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan
Ryuichi Nishii
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
Naoto Shikano
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Inashiki, Ibaraki 300-0394, Japan
Takeo Nakanishi
Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, Japan
Ikumi Tamai
Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan
Keiichi Kawai
Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
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.
