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

• Main Authors: Masato Kobayashi (Author), Asuka Mizutani (Author), Yuka Muranaka (Author), Kodai Nishi (Author), Hisakazu Komori (Author), Ryuichi Nishii (Author), Naoto Shikano (Author), Takeo Nakanishi (Author), Ikumi Tamai (Author), Keiichi Kawai (Author)
• Format: Book
• Published: MDPI AG, 2021-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

10.3390/pharmaceutics14010061
1999-4923