期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 13, 页码 4762-4767出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1113466109
关键词
in vivo chemistry; pharmacokinetics; PET imaging; intravital microscopy; pretargeting
资金
- National Institutes of Health (NIH) [P50CA86355, R01EB010011, K01EB010078, T32CA079443]
There has been intense interest in the development of selective bioorthogonal reactions or click chemistry that can proceed in live animals. Until now however, most reactions still require vast surpluses of reactants because of steep temporal and spatial concentration gradients. Using computational modeling and design of pharmacokinetically optimized reactants, we have developed a predictable method for efficient in vivo click reactions. Specifically, we show that polymer modified tetrazines (PMT) are a key enabler for in vivo bioorthogonal chemistry based on the very fast and catalyst-free [4 + 2] tetrazine/ trans-cyclooctene cycloaddition. Using fluorescent PMT for cellular resolution and F-18 labeled PMT for whole animal imaging, we show that cancer cell epitopes can be easily reacted in vivo. This generic strategy should help guide the design of future chemistries and find widespread use for different in vivo bioorthogonal applications, particularly in the biomedical sciences.
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