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

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

Automated summary

This study used whole-body imaging with [I-123]MIBG to investigate the absorption of cationic anticancer drugs and medicines in the gastrointestinal tract. The results showed different uptake mechanisms mediated by OCTN and OCT, which were affected by inhibitors L-carnitine and cimetidine. Furthermore, the accumulation of [I-123]MIBG was significantly altered in DSS-induced experimental colitis mice and mice with cimetidine loading. Therefore, [I-123]MIBG imaging can be used to estimate gastrointestinal absorption via OCTN and/or OCT in the small intestine.