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Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers
Occult bacterial infections represent a worldwide health problem. Differentiating active bacterial infection from sterile inflammation can be difficult using current imaging tools. Present clinically viable methodologies either detect morphologic changes (CT/ MR), recruitment of immune cells ((111)I...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554133/ https://www.ncbi.nlm.nih.gov/pubmed/28801560 http://dx.doi.org/10.1038/s41598-017-08415-x |
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author | Neumann, Kiel D. Villanueva-Meyer, Javier E. Mutch, Christopher A. Flavell, Robert R. Blecha, Joseph E. Kwak, Tiffany Sriram, Renuka VanBrocklin, Henry F. Rosenberg, Oren S. Ohliger, Michael A. Wilson, David M. |
author_facet | Neumann, Kiel D. Villanueva-Meyer, Javier E. Mutch, Christopher A. Flavell, Robert R. Blecha, Joseph E. Kwak, Tiffany Sriram, Renuka VanBrocklin, Henry F. Rosenberg, Oren S. Ohliger, Michael A. Wilson, David M. |
author_sort | Neumann, Kiel D. |
collection | PubMed |
description | Occult bacterial infections represent a worldwide health problem. Differentiating active bacterial infection from sterile inflammation can be difficult using current imaging tools. Present clinically viable methodologies either detect morphologic changes (CT/ MR), recruitment of immune cells ((111)In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells ((18)F-FDG PET). However, these strategies are often inadequate to detect bacterial infection and are not specific for living bacteria. Recent approaches have taken advantage of key metabolic differences between prokaryotic and eukaryotic organisms, allowing easier distinction between bacteria and their host. In this report, we exploited one key difference, bacterial cell wall biosynthesis, to detect living bacteria using a positron-labeled D-amino acid. After screening several (14)C D-amino acids for their incorporation into E. coli in culture, we identified D-methionine as a probe with outstanding radiopharmaceutical potential. Based on an analogous procedure to that used for L-[methyl-(11)C]methionine ([(11)C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl-(11)C]methionine ([(11)C] D-Met), and showed that it can rapidly and selectively differentiate both E. coli and S. aureus infections from sterile inflammation in vivo. We believe that the ease of [(11)C] D-Met radiosynthesis, coupled with its rapid and specific in vivo bacterial accumulation, make it an attractive radiotracer for infection imaging in clinical practice. |
format | Online Article Text |
id | pubmed-5554133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55541332017-08-15 Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers Neumann, Kiel D. Villanueva-Meyer, Javier E. Mutch, Christopher A. Flavell, Robert R. Blecha, Joseph E. Kwak, Tiffany Sriram, Renuka VanBrocklin, Henry F. Rosenberg, Oren S. Ohliger, Michael A. Wilson, David M. Sci Rep Article Occult bacterial infections represent a worldwide health problem. Differentiating active bacterial infection from sterile inflammation can be difficult using current imaging tools. Present clinically viable methodologies either detect morphologic changes (CT/ MR), recruitment of immune cells ((111)In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells ((18)F-FDG PET). However, these strategies are often inadequate to detect bacterial infection and are not specific for living bacteria. Recent approaches have taken advantage of key metabolic differences between prokaryotic and eukaryotic organisms, allowing easier distinction between bacteria and their host. In this report, we exploited one key difference, bacterial cell wall biosynthesis, to detect living bacteria using a positron-labeled D-amino acid. After screening several (14)C D-amino acids for their incorporation into E. coli in culture, we identified D-methionine as a probe with outstanding radiopharmaceutical potential. Based on an analogous procedure to that used for L-[methyl-(11)C]methionine ([(11)C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl-(11)C]methionine ([(11)C] D-Met), and showed that it can rapidly and selectively differentiate both E. coli and S. aureus infections from sterile inflammation in vivo. We believe that the ease of [(11)C] D-Met radiosynthesis, coupled with its rapid and specific in vivo bacterial accumulation, make it an attractive radiotracer for infection imaging in clinical practice. Nature Publishing Group UK 2017-08-11 /pmc/articles/PMC5554133/ /pubmed/28801560 http://dx.doi.org/10.1038/s41598-017-08415-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Neumann, Kiel D. Villanueva-Meyer, Javier E. Mutch, Christopher A. Flavell, Robert R. Blecha, Joseph E. Kwak, Tiffany Sriram, Renuka VanBrocklin, Henry F. Rosenberg, Oren S. Ohliger, Michael A. Wilson, David M. Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers |
title | Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers |
title_full | Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers |
title_fullStr | Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers |
title_full_unstemmed | Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers |
title_short | Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers |
title_sort | imaging active infection in vivo using d-amino acid derived pet radiotracers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554133/ https://www.ncbi.nlm.nih.gov/pubmed/28801560 http://dx.doi.org/10.1038/s41598-017-08415-x |
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