Development of radioiodine-labeled mequitazine for evaluation of hepatic CYP2D activity.

Autor:	Mizutani A; Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan., Kobayashi M; Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan., Nishi K; Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan., Fujita KI; Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, Showa University School of Pharmacy, Tokyo, Japan., Takahashi K; Department of Radiologic Technology, National Cancer Center Hospital East, Kashiwa, Japan., Muranaka Y; Department of Radiological Technology, Faculty of Health Science, Juntendo University, Tokyo, Japan., Sato K; Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Kitamura M; Faculty of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Japan., Suzuki C; Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan., Nishii R; Department of Integrated Health Sciences, Graduate School of Medicine, Nagoya University, Nagoya, Japan., Shikano N; Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan., Magata Y; Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan., Ishida Y; Department of Psychiatry, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan., Kunishima M; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan., Fukuchi K; Division of Medical Technology and Science, Department of Medical Physics and Engineering, Course of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan., Kawai K; Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.; Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 Jun 19; Vol. 15, pp. 1397288. Date of Electronic Publication: 2024 Jun 19 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1397288
Abstrakt:	Background: 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. Methods: Iodine-123- and 125-labeled 4-iodobenzylmequitazine ( 123/125 I-BMQ) was synthesized with high labeling and purity. CYP isozymes involved in the metabolism of 125 I-BMQ in mouse liver microsomes were evaluated, and the utility of 123/125 I-was assessed from biological distribution and SPECT imaging evaluation in normal and CYP2D-inhibited mice. Results: In vitro metabolite analysis using mouse liver microsomes showed that 125 I-BMQ is specifically metabolized by CYP2D. 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. Conclusion: 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Mizutani, Kobayashi, Nishi, Fujita, Takahashi, Muranaka, Sato, Kitamura, Suzuki, Nishii, Shikano, Magata, Ishida, Kunishima, Fukuchi and Kawai.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu