AUTHOR=Mizutani Asuka , Kobayashi Masato , Nishi Kodai , Fujita Ken-ichi , Takahashi Kotaro , Muranaka Yuka , Sato Kakeru , Kitamura Masanori , Suzuki Chie , Nishii Ryuichi , Shikano Naoto , Magata Yasuhiro , Ishida Yasushi , Kunishima Munetaka , Fukuchi Kazuki , Kawai Keiichi 

TITLE=Development of radioiodine-labeled mequitazine for evaluation of hepatic CYP2D activity

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1397288

DOI=10.3389/fphar.2024.1397288

ISSN=1663-9812

ABSTRACT=As drug-metabolizing enzyme activities are affected by a variety of factors, such as drug-drug interactions, a method to evaluate drug-metabolizing enzyme activities in real time is needed. In this study, we developed a novel SPECT imaging probe for evaluation of hepatic CYP2D activity. Iodine-123-and 125-labeled 4-iodobenzylmequitazine ( 123/125 I-BMQ) was obtained with high labeling and purity, and CYP2D alone played a significant role in its metabolism. Biological distribution and SPECT imaging of 123/125 I-BMQ in normal mice showed that injection 123/125 I-BMQ accumulated early in the liver and was excreted into the gallbladder and intestines. In CYP2D-inhibited mice, accumulation in the liver was increased, but accumulation in the gallbladder and intestines, the excretory organ, was delayed. Since only metabolites of 125 I-BMQ are detected in bile, visualization and measuring of the accumulation of metabolites over time in the intestine, where bile is excreted, could predict the amount of metabolites produced in the body and evaluate CYP2D activity, which would be useful in determining the dosage of various drugs metabolized by CYP2D. Therefore, 123/125 I-BMQ is useful as a SPECT imaging probe for comprehensive and direct assessment of hepatic CYP2D activity in a minimally invasive and simple approach.