Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis
Abstract Background Vertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomograph...
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| Veröffentlicht in: | The Journal of infectious diseases 2023-10, Vol.228 (Supplement_4), p.S281-S290 |
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| creator | Parker, Matthew F L López-Álvarez, Marina Alanizi, Aryn A Luu, Justin M Polvoy, Ilona Sorlin, Alexandre M Qin, Hecong Lee, Sanghee Rabbitt, Sarah J Pichardo-González, Priamo A Ordonez, Alvaro A Blecha, Joseph Rosenberg, Oren S Flavell, Robert R Engel, Joanne Jain, Sanjay K Ohliger, Michael A Wilson, David M |
| description | Abstract
Background
Vertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported.
Methods
We compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli.
Results
In the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS.
Conclusions
Our work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO. |
| doi_str_mv | 10.1093/infdis/jiad159 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2872807515</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/infdis/jiad159</oup_id><sourcerecordid>3041069017</sourcerecordid><originalsourceid>FETCH-LOGICAL-c357t-5161a04784fc7b1992c2824fa64f2907cd2a882aaa050cda4e51cd94da30fa063</originalsourceid><addsrcrecordid>eNqFkU1vEzEQhi0EomngyhFZ4kIP2469H_YeUUkBqVWjKnBdTezZxNHuOtjeSvkP_Gg2SuDAhdN86JlXM_My9k7AtYA6v3FDa1282Tm0oqxfsJkoc5VVlchfshmAlJnQdX3BLmPcAUCRV-o1u8iV0rqEcsZ-LZ6xGzG5YcPTlviSQutDj4Mh7lu-xLT1GxqyFYYNJbJ86aNLwQ980bsY3ZSsfO83AffbA39C63wKaChE7gaOUyfxB2-pO6r9oJBoHbDjn100LrmYPcZEvj9Qd6zesFctdpHenuOcfb9brG6_ZvePX77dfrrPTF6qlJWiEgiF0kVr1FrUtTRSy6LFqmhlDcpYiVpLRIQSjMWCSmFsXVjMoUWo8jn7eNLdB_9zpJia6RZDXYcD-TE2UiupQZXTL-fswz_ozo9hmLZrcigEVDUINVHXJ8oEH2OgttkH12M4NAKao0_Nyafm7NM08P4sO657sn_xP8ZMwNUJ8OP-f2K_AdDkoNE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3041069017</pqid></control><display><type>article</type><title>Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Parker, Matthew F L ; López-Álvarez, Marina ; Alanizi, Aryn A ; Luu, Justin M ; Polvoy, Ilona ; Sorlin, Alexandre M ; Qin, Hecong ; Lee, Sanghee ; Rabbitt, Sarah J ; Pichardo-González, Priamo A ; Ordonez, Alvaro A ; Blecha, Joseph ; Rosenberg, Oren S ; Flavell, Robert R ; Engel, Joanne ; Jain, Sanjay K ; Ohliger, Michael A ; Wilson, David M</creator><creatorcontrib>Parker, Matthew F L ; López-Álvarez, Marina ; Alanizi, Aryn A ; Luu, Justin M ; Polvoy, Ilona ; Sorlin, Alexandre M ; Qin, Hecong ; Lee, Sanghee ; Rabbitt, Sarah J ; Pichardo-González, Priamo A ; Ordonez, Alvaro A ; Blecha, Joseph ; Rosenberg, Oren S ; Flavell, Robert R ; Engel, Joanne ; Jain, Sanjay K ; Ohliger, Michael A ; Wilson, David M</creatorcontrib><description>Abstract
Background
Vertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported.
Methods
We compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli.
Results
In the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS.
Conclusions
Our work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiad159</identifier><identifier>PMID: 37788505</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>4-Aminobenzoic Acid ; Animal models ; Animals ; Bacteria ; Bacterial infections ; Computed tomography ; Discitis ; Discitis - diagnostic imaging ; Escherichia coli ; Humans ; Magnetic resonance imaging ; Osteomyelitis ; Osteomyelitis - microbiology ; Pathogens ; Positron emission tomography ; Positron-Emission Tomography - methods ; Radioactive tracers ; Radiopharmaceuticals ; Rats ; Spine ; Staphylococcal Infections - diagnostic imaging ; Staphylococcus aureus ; Tomography ; Vertebrae</subject><ispartof>The Journal of infectious diseases, 2023-10, Vol.228 (Supplement_4), p.S281-S290</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-5161a04784fc7b1992c2824fa64f2907cd2a882aaa050cda4e51cd94da30fa063</citedby><cites>FETCH-LOGICAL-c357t-5161a04784fc7b1992c2824fa64f2907cd2a882aaa050cda4e51cd94da30fa063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37788505$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Parker, Matthew F L</creatorcontrib><creatorcontrib>López-Álvarez, Marina</creatorcontrib><creatorcontrib>Alanizi, Aryn A</creatorcontrib><creatorcontrib>Luu, Justin M</creatorcontrib><creatorcontrib>Polvoy, Ilona</creatorcontrib><creatorcontrib>Sorlin, Alexandre M</creatorcontrib><creatorcontrib>Qin, Hecong</creatorcontrib><creatorcontrib>Lee, Sanghee</creatorcontrib><creatorcontrib>Rabbitt, Sarah J</creatorcontrib><creatorcontrib>Pichardo-González, Priamo A</creatorcontrib><creatorcontrib>Ordonez, Alvaro A</creatorcontrib><creatorcontrib>Blecha, Joseph</creatorcontrib><creatorcontrib>Rosenberg, Oren S</creatorcontrib><creatorcontrib>Flavell, Robert R</creatorcontrib><creatorcontrib>Engel, Joanne</creatorcontrib><creatorcontrib>Jain, Sanjay K</creatorcontrib><creatorcontrib>Ohliger, Michael A</creatorcontrib><creatorcontrib>Wilson, David M</creatorcontrib><title>Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
Background
Vertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported.
Methods
We compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli.
Results
In the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS.
Conclusions
Our work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO.</description><subject>4-Aminobenzoic Acid</subject><subject>Animal models</subject><subject>Animals</subject><subject>Bacteria</subject><subject>Bacterial infections</subject><subject>Computed tomography</subject><subject>Discitis</subject><subject>Discitis - diagnostic imaging</subject><subject>Escherichia coli</subject><subject>Humans</subject><subject>Magnetic resonance imaging</subject><subject>Osteomyelitis</subject><subject>Osteomyelitis - microbiology</subject><subject>Pathogens</subject><subject>Positron emission tomography</subject><subject>Positron-Emission Tomography - methods</subject><subject>Radioactive tracers</subject><subject>Radiopharmaceuticals</subject><subject>Rats</subject><subject>Spine</subject><subject>Staphylococcal Infections - diagnostic imaging</subject><subject>Staphylococcus aureus</subject><subject>Tomography</subject><subject>Vertebrae</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EomngyhFZ4kIP2469H_YeUUkBqVWjKnBdTezZxNHuOtjeSvkP_Gg2SuDAhdN86JlXM_My9k7AtYA6v3FDa1282Tm0oqxfsJkoc5VVlchfshmAlJnQdX3BLmPcAUCRV-o1u8iV0rqEcsZ-LZ6xGzG5YcPTlviSQutDj4Mh7lu-xLT1GxqyFYYNJbJ86aNLwQ980bsY3ZSsfO83AffbA39C63wKaChE7gaOUyfxB2-pO6r9oJBoHbDjn100LrmYPcZEvj9Qd6zesFctdpHenuOcfb9brG6_ZvePX77dfrrPTF6qlJWiEgiF0kVr1FrUtTRSy6LFqmhlDcpYiVpLRIQSjMWCSmFsXVjMoUWo8jn7eNLdB_9zpJia6RZDXYcD-TE2UiupQZXTL-fswz_ozo9hmLZrcigEVDUINVHXJ8oEH2OgttkH12M4NAKao0_Nyafm7NM08P4sO657sn_xP8ZMwNUJ8OP-f2K_AdDkoNE</recordid><startdate>20231003</startdate><enddate>20231003</enddate><creator>Parker, Matthew F L</creator><creator>López-Álvarez, Marina</creator><creator>Alanizi, Aryn A</creator><creator>Luu, Justin M</creator><creator>Polvoy, Ilona</creator><creator>Sorlin, Alexandre M</creator><creator>Qin, Hecong</creator><creator>Lee, Sanghee</creator><creator>Rabbitt, Sarah J</creator><creator>Pichardo-González, Priamo A</creator><creator>Ordonez, Alvaro A</creator><creator>Blecha, Joseph</creator><creator>Rosenberg, Oren S</creator><creator>Flavell, Robert R</creator><creator>Engel, Joanne</creator><creator>Jain, Sanjay K</creator><creator>Ohliger, Michael A</creator><creator>Wilson, David M</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20231003</creationdate><title>Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis</title><author>Parker, Matthew F L ; López-Álvarez, Marina ; Alanizi, Aryn A ; Luu, Justin M ; Polvoy, Ilona ; Sorlin, Alexandre M ; Qin, Hecong ; Lee, Sanghee ; Rabbitt, Sarah J ; Pichardo-González, Priamo A ; Ordonez, Alvaro A ; Blecha, Joseph ; Rosenberg, Oren S ; Flavell, Robert R ; Engel, Joanne ; Jain, Sanjay K ; Ohliger, Michael A ; Wilson, David M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-5161a04784fc7b1992c2824fa64f2907cd2a882aaa050cda4e51cd94da30fa063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>4-Aminobenzoic Acid</topic><topic>Animal models</topic><topic>Animals</topic><topic>Bacteria</topic><topic>Bacterial infections</topic><topic>Computed tomography</topic><topic>Discitis</topic><topic>Discitis - diagnostic imaging</topic><topic>Escherichia coli</topic><topic>Humans</topic><topic>Magnetic resonance imaging</topic><topic>Osteomyelitis</topic><topic>Osteomyelitis - microbiology</topic><topic>Pathogens</topic><topic>Positron emission tomography</topic><topic>Positron-Emission Tomography - methods</topic><topic>Radioactive tracers</topic><topic>Radiopharmaceuticals</topic><topic>Rats</topic><topic>Spine</topic><topic>Staphylococcal Infections - diagnostic imaging</topic><topic>Staphylococcus aureus</topic><topic>Tomography</topic><topic>Vertebrae</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Parker, Matthew F L</creatorcontrib><creatorcontrib>López-Álvarez, Marina</creatorcontrib><creatorcontrib>Alanizi, Aryn A</creatorcontrib><creatorcontrib>Luu, Justin M</creatorcontrib><creatorcontrib>Polvoy, Ilona</creatorcontrib><creatorcontrib>Sorlin, Alexandre M</creatorcontrib><creatorcontrib>Qin, Hecong</creatorcontrib><creatorcontrib>Lee, Sanghee</creatorcontrib><creatorcontrib>Rabbitt, Sarah J</creatorcontrib><creatorcontrib>Pichardo-González, Priamo A</creatorcontrib><creatorcontrib>Ordonez, Alvaro A</creatorcontrib><creatorcontrib>Blecha, Joseph</creatorcontrib><creatorcontrib>Rosenberg, Oren S</creatorcontrib><creatorcontrib>Flavell, Robert R</creatorcontrib><creatorcontrib>Engel, Joanne</creatorcontrib><creatorcontrib>Jain, Sanjay K</creatorcontrib><creatorcontrib>Ohliger, Michael A</creatorcontrib><creatorcontrib>Wilson, David M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Parker, Matthew F L</au><au>López-Álvarez, Marina</au><au>Alanizi, Aryn A</au><au>Luu, Justin M</au><au>Polvoy, Ilona</au><au>Sorlin, Alexandre M</au><au>Qin, Hecong</au><au>Lee, Sanghee</au><au>Rabbitt, Sarah J</au><au>Pichardo-González, Priamo A</au><au>Ordonez, Alvaro A</au><au>Blecha, Joseph</au><au>Rosenberg, Oren S</au><au>Flavell, Robert R</au><au>Engel, Joanne</au><au>Jain, Sanjay K</au><au>Ohliger, Michael A</au><au>Wilson, David M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2023-10-03</date><risdate>2023</risdate><volume>228</volume><issue>Supplement_4</issue><spage>S281</spage><epage>S290</epage><pages>S281-S290</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><abstract>Abstract
Background
Vertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported.
Methods
We compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli.
Results
In the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS.
Conclusions
Our work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>37788505</pmid><doi>10.1093/infdis/jiad159</doi></addata></record> |
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| ispartof | The Journal of infectious diseases, 2023-10, Vol.228 (Supplement_4), p.S281-S290 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | 4-Aminobenzoic Acid Animal models Animals Bacteria Bacterial infections Computed tomography Discitis Discitis - diagnostic imaging Escherichia coli Humans Magnetic resonance imaging Osteomyelitis Osteomyelitis - microbiology Pathogens Positron emission tomography Positron-Emission Tomography - methods Radioactive tracers Radiopharmaceuticals Rats Spine Staphylococcal Infections - diagnostic imaging Staphylococcus aureus Tomography Vertebrae |
| title | Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis |
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