Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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
_version_ 1783256730708213760
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
work_keys_str_mv AT neumannkield imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT villanuevameyerjaviere imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT mutchchristophera imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT flavellrobertr imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT blechajosephe imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT kwaktiffany imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT sriramrenuka imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT vanbrocklinhenryf imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT rosenbergorens imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT ohligermichaela imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers
AT wilsondavidm imagingactiveinfectioninvivousingdaminoacidderivedpetradiotracers