123I-BMIPP, a Radiopharmaceutical for Myocardial Fatty Acid Metabolism Scintigraphy, Could Be Utilized in Bacterial Infection Imaging

Yuka Muranaka; Asuka Mizutani; Masato Kobayashi; Koya Nakamoto; Miki Matsue; Fumika Takagi; Kenichi Okazaki; Kodai Nishi; Kana Yamazaki; Ryuichi Nishii; Naoto Shikano; Shigefumi Okamoto; Hideki Maki; Keiichi Kawai

doi:10.3390/pharmaceutics14051008

¹²³I-BMIPP, a Radiopharmaceutical for Myocardial Fatty Acid Metabolism Scintigraphy, Could Be Utilized in Bacterial Infection Imaging

Pharmaceutics. 2022 May 7;14(5):1008. doi: 10.3390/pharmaceutics14051008.

Authors

Yuka Muranaka¹, Asuka Mizutani², Masato Kobayashi², Koya Nakamoto¹, Miki Matsue³, Fumika Takagi⁴, Kenichi Okazaki⁴, Kodai Nishi⁵, Kana Yamazaki⁶, Ryuichi Nishii⁶, Naoto Shikano⁷, Shigefumi Okamoto^{2

8}, Hideki Maki⁴, Keiichi Kawai^{1

9}

Affiliations

¹ Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan.
² Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan.
³ Ishikawa Prefectural Institute of Public Health and Environmental Science, 1-11, Taiyogaoka, Kanazawa 920-1154, Japan.
⁴ Laboratory for Drug Discovery & Disease Research, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka 561-0825, Japan.
⁵ Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
⁶ Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
⁷ Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Inashiki 300-0394, Japan.
⁸ Advanced Health Care Science Research Unit, Innovative Integrated Bio-Research Core Institute for Frontier Science Initiative, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan.
⁹ Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuoka-shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.

Abstract

In this study, we evaluated the use of 15-(4-¹²³I-iodophenyl)-3(R,S)-methylpentadecanoic acid (¹²³I-BMIPP) to visualize fatty acid metabolism in bacteria for bacterial infection imaging. We found that ¹²³I-BMIPP, which is used for fatty acid metabolism scintigraphy in Japan, accumulated markedly in Escherichia coli EC-14 similar to ¹⁸F-FDG, which has previously been studied for bacterial imaging. To elucidate the underlying mechanism, we evaluated changes in ¹²³I-BMIPP accumulation under low-temperature conditions and in the presence of a CD36 inhibitor. The uptake of ¹²³I-BMIPP by EC-14 was mediated via the CD36-like fatty-acid-transporting membrane protein and accumulated by fatty acid metabolism. In model mice infected with EC-14, the biological distribution and whole-body imaging were assessed using ¹²³I-BMIPP and ¹⁸F-FDG. The ¹²³I-BMIPP biodistribution study showed that, 8 h after infection, the ratio of ¹²³I-BMIPP accumulated in infected muscle to that in control muscle was 1.31 at 60 min after ¹²³I-BMIPP injection. In whole-body imaging 1.5 h after ¹²³I-BMIPP administration and 9.5 h after infection, infected muscle exhibited a 1.33-times higher contrast than non-infected muscle. Thus, ¹²³I-BMIPP shows potential for visualizing fatty acid metabolism of bacteria for imaging bacterial infections.

Keywords: 123I-BMIPP; SPECT; bacterial imaging; bacterial infection; nuclear medicine imaging.

Abstract

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