{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:57:28Z","timestamp":1792799848051,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Suspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[<jats:sup>18<\/jats:sup>F] fluoro-D-glucose: [<jats:sup>18<\/jats:sup>F]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We tested two specific radiotracers: 2-deoxy-2-[<jats:sup>18<\/jats:sup>F]-fluoro-D-sorbitol ([<jats:sup>18<\/jats:sup>F]FDS) and 2-[<jats:sup>18<\/jats:sup>F]F-\u03c1-aminobenzoic acid ([<jats:sup>18<\/jats:sup>F]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested <jats:italic>in vitro<\/jats:italic> and in an experimental mouse model of myositis infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Non-lactose fermenters (<jats:italic>Pseudomonas aeruginosa<\/jats:italic> and <jats:italic>Stenotrophomonas maltophilia<\/jats:italic>) were unable to take up [<jats:sup>18<\/jats:sup>F]FDG <jats:italic>in vitro<\/jats:italic>. [<jats:sup>18<\/jats:sup>F]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., <jats:italic>Candida albicans<\/jats:italic> vs. <jats:italic>Candida glabrata<\/jats:italic>). All bacteria and yeasts tested were detected <jats:italic>in vitro<\/jats:italic> by [<jats:sup>18<\/jats:sup>F]FPABA. Furthermore, [<jats:sup>18<\/jats:sup>F]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (<jats:italic>E. coli<\/jats:italic> and <jats:italic>Staphylococcus aureus<\/jats:italic>) and could be used as a probe for a wide variety of bacterial and fungal species.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1094929","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T10:34:10Z","timestamp":1674642850000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Infection-specific PET imaging with 18F-fluorodeoxysorbitol and 2-[18F]F-\u03c1-aminobenzoic acid: An extended diagnostic tool for bacterial and fungal diseases"],"prefix":"10.3389","volume":"14","author":[{"given":"Marta","family":"Rua","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon Ander","family":"Sim\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Collantes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Ecay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Leiva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Carmona-Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix","family":"Pareja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna R.","family":"Pulagam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Llop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Del Pozo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Pe\u00f1uelas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/diagnostics11010137","article-title":"The added value of [18 f]fdg pet\/ct in the management of invasive fungal infections","volume":"11","author":"Ankrah","year":"2021","journal-title":"Diagnostics"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8020197","article-title":"PET radiopharmaceuticals for specific bacteria imaging: a systematic review","volume":"8","author":"Auletta","year":"2019","journal-title":"J. Clin. Med."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/bies.10114","article-title":"The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery","volume":"24","author":"Bermingham","year":"2002","journal-title":"BioEssays"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.ejvs.2019.10.016","article-title":"Editor\u2019s choice\u2014European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections","volume":"59","author":"Chakf\u00e9","year":"2020","journal-title":"Eur. J. Vas. Endovasc. Surg."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"153601212093687","DOI":"10.1177\/1536012120936876","article-title":"Evaluation of musculoskeletal and pulmonary bacterial infections with [124I]FIAU PET\/CT","volume":"19","author":"Cho","year":"2020","journal-title":"Mol. Imaging"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1146\/annurev.ge.10.120176.002013","article-title":"Genetics of the bacterial phosphoenolpyruvate: glycose phosphotransferase system","volume":"10","author":"Cordaro","year":"1976","journal-title":"Annu. Rev. Genet."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1093\/jac\/20.5.639","article-title":"The inoculum effect with gram-negative bacteria in vitro and in vivo","volume":"20","author":"Davey","year":"1987","journal-title":"J. Antimicrob. Chemother."},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00374-20","article-title":"Dihydrofolate Reductase is a valid target for antifungal development in the human pathogen Candida albicans","volume":"5","author":"DeJarnette","year":"2020","journal-title":"mSphere"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1002\/pro.2820","article-title":"The AbgT family: a novel class of antimetabolite transporters","volume":"25","author":"Delmar","year":"2016","journal-title":"Protein Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1080\/20014091096710","article-title":"A metabolic node in action: chorismate-utilizing enzymes in microorganisms","volume":"27","author":"Dosselaere","year":"2001","journal-title":"Crit. Rev. Microbiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/S1474-4422(14)70090-0","article-title":"Advancing research diagnostic criteria for Alzheimer\u2019s disease: the IWG-2 criteria","volume":"13","author":"Dubois","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1016\/j.jcmg.2020.02.033","article-title":"Radiolabeled-white blood cell imaging in cardiac device-related infective endocarditis: worth all the effort?","volume":"13","author":"Erba","year":"2020","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s15010-018-1152-2","article-title":"Neuroinfections caused by fungi","volume":"46","author":"G\u00f3ralska","year":"2018","journal-title":"Infection"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1007\/s00259-021-05603-w","article-title":"EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3","volume":"49","author":"Guedj","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"3075","DOI":"10.1093\/eurheartj\/ehv319","article-title":"2015 ESC Guidelines for the management of infective endocarditis: the task force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European","volume":"36","author":"Habib","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1056\/NEJMra2111003","article-title":"Fever of unknown origin","volume":"386","author":"Haidar","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"465","DOI":"10.3109\/02713689408999875","article-title":"Growth curve for Propionibacterium acnes","volume":"13","author":"Hall","year":"1994","journal-title":"Curr. Eye Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"4973","DOI":"10.1038\/s41598-017-05403-z","article-title":"In vitro imaging of bacteria using 18F-fluorodeoxyglucose micro positron emission tomography","volume":"7","author":"Heuker","year":"2017","journal-title":"Sci. Rep."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1111\/myc.13148","article-title":"Breakthrough invasive fungal infections: who is at risk?","volume":"63","author":"Jenks","year":"2020","journal-title":"Mycoses"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms6427","article-title":"Rapid detection of single bacteria in unprocessed blood using integrated comprehensive droplet digital detection","volume":"5","author":"Kang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"584741","DOI":"10.3389\/fped.2021.584741","article-title":"Case report: (18)F-FDG PET-CT for diagnosing prosthetic device-related infection in an infant with CHD","volume":"9","author":"Kawamura","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-022-29553-5","article-title":"In vivo imaging of invasive aspergillosis with 18F-fluorodeoxysorbitol positron emission tomography","volume":"13","author":"Kim","year":"2022","journal-title":"Nat. Commun."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1093\/jac\/42.2.227","article-title":"Bacterial concentrations in pus and infected peritoneal fluid - implications for bactericidal activity of antibiotics","volume":"42","author":"K\u00f6nig","year":"1998","journal-title":"J. Antimicrob. Chemother."},{"key":"ref24","first-page":"915","article-title":"Summary of species characteristics","volume-title":"The Yeasts","author":"Kurtzman","year":"1998"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1007\/s00259-008-0887-x","article-title":"FDG-PET for diagnosing prosthetic joint infection: systematic review and metaanalysis","volume":"35","author":"Kwee","year":"2008","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3390\/jof8010025","article-title":"Evaluation of 2-[18F]-Fluorodeoxysorbitol PET imaging in preclinical models of Aspergillus infection","volume":"8","author":"Lai","year":"2022","journal-title":"J. Fungi"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"3430","DOI":"10.1007\/s00259-022-05769-x","article-title":"Evidence-based guideline of the European Association of Nuclear Medicine (EANM) on imaging infection in vascular grafts","volume":"49","author":"Lauri","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1128\/jb.124.1.39-47.1975","article-title":"Nature and properties of hexitol transport systems in Escherichia coli","volume":"124","author":"Lengeler","year":"1975","journal-title":"J. Bacteriol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1021\/acsinfecdis.0c00374","article-title":"Positron emission tomography imaging of Staphylococcus aureus infection using a nitro-Prodrug analogue of 2-[18F]F-p-Aminobenzoic acid","volume":"6","author":"Li","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1007\/s11307-007-0125-0","article-title":"The synthesis of 18F-FDS and its potential application in molecular imaging","volume":"10","author":"Li","year":"2008","journal-title":"Mol. Imaging Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"195420","DOI":"10.2967\/jnumed.117.195420","article-title":"Validation of 2-18 F-fluorodeoxysorbitol (18 F-FDS) as a potential radiopharmaceutical for imaging bacterial infection in the lung","volume":"59","author":"Li","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1007\/s12350-017-1092-8","article-title":"Meta-analysis of 18F-FDG PET\/CT in the diagnosis of infective endocarditis","volume":"26","author":"Mahmood","year":"2019","journal-title":"J. Nucl. Cardiol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.cell.2020.10.022","article-title":"Emerging pandemic diseases: how we got to COVID-19","volume":"183","author":"Morens","year":"2020","journal-title":"Cells"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/jci.insight.154117","article-title":"11C-Para-aminobenzoic acid PET imaging of S. aureus and MRSA infection in preclinical models and humans","volume":"7","author":"Ordonez","year":"2022","journal-title":"JCI Insight"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"144","DOI":"10.2967\/jnumed.116.181792","article-title":"A systematic approach for developing bacteria-specific imaging tracers","volume":"58","author":"Ordonez","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abe9805","article-title":"Imaging Enterobacterales infections in patients using pathogen-specific positron emission tomography","volume":"13","author":"Ordonez","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1007\/s00259-020-04948-y","article-title":"(68)Ga-labelled desferrioxamine-B for bacterial infection imaging","volume":"48","author":"Petrik","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3322\/caac.21713","article-title":"Molecular imaging in oncology: current impact and future directions","volume":"72","author":"Rowe","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1086\/592973","article-title":"Prolonged bacterial culture to identify late periprosthetic joint infection: a promising strategy","volume":"47","author":"Sch\u00e4fer","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s41824-022-00138-1","article-title":"A role for artificial intelligence in molecular imaging of infection and inflammation","volume":"6","author":"Schwenck","year":"2022","journal-title":"Eur. J. Hybrid Imag."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1038\/s41598-020-80213-4","article-title":"Mutations of folC cause increased susceptibility to sulfamethoxazole in mycobacterium tuberculosis","volume":"11","author":"Wang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"259ra146","DOI":"10.1126\/scitranslmed.3009815","article-title":"Imaging enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography","volume":"6","author":"Weinstein","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.nucmedbio.2015.11.008","article-title":"Infection imaging with 18F-FDS and first-in-human evaluation","volume":"43","author":"Yao","year":"2016","journal-title":"Nucl. Med. Biol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.chemosphere.2007.07.045","article-title":"A mechanistical model for the uptake of sulfonamides by bacteria","volume":"70","author":"Zarfl","year":"2008","journal-title":"Chemosphere"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1021\/acsinfecdis.8b00182","article-title":"Positron emission tomography imaging with 2-[18F]F- p-Aminobenzoic acid detects Staphylococcus aureus infections and monitors drug response","volume":"4","author":"Zhang","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1007\/s11307-016-0946-9","article-title":"Biodistribution and radiation Dosimetry of the Enterobacteriaceae -specific imaging probe [18 F] Fluorodeoxysorbitol determined by PET\/CT in healthy human volunteers","volume":"18","author":"Zhu","year":"2016","journal-title":"Mol. Imaging Biol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1094929\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T10:34:13Z","timestamp":1674642853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1094929\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":46,"alternative-id":["10.3389\/fmicb.2023.1094929"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1094929","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,25]]},"article-number":"1094929"}}