Abstract |
Biosorption-based bacterial 64Cu-labeling and its application in pharmacokinetic positron-emission tomography (PET) were investigated. Both gram-positive and gram-negative bacteria were efficiently labeled with [64Cu]Cu2+ ion in saline at room temperature within 5 min. The labeling ratio for Escherichia coli drastically decreased with trypsin pretreatment and the co-presence of excess Cu2+ ion, indicating the existence of specific Cu2+ binding sites on the E. coli cell surface. Washing with lysogeny broth medium was effective in purifying 64Cu-labeled E. coli for kinetic study; the labeling stability was approximately 90% in serum for 15 min. According to dynamic PET imaging in colon-26 tumor-bearing mice, 64Cu-labeled E. coli immediately disappeared from the blood circulation and primarily accumulated in the liver. In addition, transient pulmonary distribution was observed, being in a dose-dependently accelerated manner. Considering the simplicity and versatility of biosorption-based bacterial 64Cu-labeling without genetic modification, the early-phase pharmacokinetic PET with 64Cu-labeled bacteria is promising for assessing toxicological aspects of bacteria-mediated cancer therapy as well as a variety of bacterial pathogenicities in infectious diseases.
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Authors | Shoko Nomura, Maiko Takahashi, Akari Hashiba Kato, Yasuhiro Wada, Yasuyoshi Watanabe, Fumiyoshi Yamashita, Hidefumi Mukai |
Journal | International journal of pharmaceutics
(Int J Pharm)
Vol. 590
Pg. 119950
(Nov 30 2020)
ISSN: 1873-3476 [Electronic] Netherlands |
PMID | 33027635
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 Elsevier B.V. All rights reserved. |
Chemical References |
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Topics |
- Animals
- Anti-Bacterial Agents
- Cell Line, Tumor
- Escherichia coli
- Gram-Negative Bacteria
- Gram-Positive Bacteria
- Mice
- Positron-Emission Tomography
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