Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers

Abstract 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 cell...

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Autores principales:	Kiel D. Neumann, Javier E. Villanueva-Meyer, Christopher A. Mutch, Robert R. Flavell, Joseph E. Blecha, Tiffany Kwak, Renuka Sriram, Henry F. VanBrocklin, Oren S. Rosenberg, Michael A. Ohliger, David M. Wilson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/98560c85b2d34a00acba4335bac177d2
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spelling	oai:doaj.org-article:98560c85b2d34a00acba4335bac177d22021-12-02T11:52:43ZImaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers10.1038/s41598-017-08415-x2045-2322https://doaj.org/article/98560c85b2d34a00acba4335bac177d22017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08415-xhttps://doaj.org/toc/2045-2322Abstract 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 (111In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells (18F-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 14C 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-11C]methionine ([11C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl-11C]methionine ([11C] 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 [11C] D-Met radiosynthesis, coupled with its rapid and specific in vivo bacterial accumulation, make it an attractive radiotracer for infection imaging in clinical practice.Kiel D. NeumannJavier E. Villanueva-MeyerChristopher A. MutchRobert R. FlavellJoseph E. BlechaTiffany KwakRenuka SriramHenry F. VanBrocklinOren S. RosenbergMichael A. OhligerDavid M. WilsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kiel D. Neumann Javier E. Villanueva-Meyer Christopher A. Mutch Robert R. Flavell Joseph E. Blecha Tiffany Kwak Renuka Sriram Henry F. VanBrocklin Oren S. Rosenberg Michael A. Ohliger David M. Wilson Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers
description	Abstract 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 (111In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells (18F-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 14C 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-11C]methionine ([11C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl-11C]methionine ([11C] 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 [11C] 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	article
author	Kiel D. Neumann Javier E. Villanueva-Meyer Christopher A. Mutch Robert R. Flavell Joseph E. Blecha Tiffany Kwak Renuka Sriram Henry F. VanBrocklin Oren S. Rosenberg Michael A. Ohliger David M. Wilson
author_facet	Kiel D. Neumann Javier E. Villanueva-Meyer Christopher A. Mutch Robert R. Flavell Joseph E. Blecha Tiffany Kwak Renuka Sriram Henry F. VanBrocklin Oren S. Rosenberg Michael A. Ohliger David M. Wilson
author_sort	Kiel D. Neumann
title	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_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_sort	imaging active infection in vivo using d-amino acid derived pet radiotracers
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/98560c85b2d34a00acba4335bac177d2
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Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers

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