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Radiolabelled <jats:sc>d<\/jats:sc>-amino acids are promising candidates because they are actively incorporated into the peptidoglycan of the bacterial cell wall, a structural feature which is absent in human cells. This work describes fluorine-18 labelled analogues of <jats:sc>d<\/jats:sc>-tyrosine and <jats:sc>d<\/jats:sc>-methionine, <jats:italic>O<\/jats:italic>-(2-[<jats:sup>18<\/jats:sup>F]fluoroethyl)-<jats:sc>d<\/jats:sc>-tyrosine (<jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FET) and <jats:italic>S<\/jats:italic>-(3-[<jats:sup>18<\/jats:sup>F]fluoropropyl)-<jats:sc>d<\/jats:sc>-homocysteine (<jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FPHCys), and their pilot evaluation studies as potential radiotracers for imaging bacterial infection.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Procedures<\/jats:title>\n                <jats:p><jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FET and <jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FPHCys were prepared in classical fluorination-deprotection reactions, and their uptake in <jats:italic>Staphylococcus aureus<\/jats:italic> and <jats:italic>Pseudomonas aeruginosa<\/jats:italic> was evaluated over 2\u00a0h. Heat killed bacteria were used as controls. A clinically-relevant foreign body model of <jats:italic>S. aureus<\/jats:italic> infection was established in Balb\/c mice, as well as a sterile foreign body to mimic inflammation. The <jats:italic>ex vivo<\/jats:italic> biodistribution of <jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FPHCys in the infected and inflamed mice was evaluated after 1\u00a0h, by dissection and gamma counting. The uptake was compared to that of [<jats:sup>18<\/jats:sup>F]FDG.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p><jats:italic>In vitro<\/jats:italic> uptake of both <jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FET and <jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FPHCys was specific to live bacteria. Uptake was higher in <jats:italic>S. aureus<\/jats:italic> than in <jats:italic>P. aeruginosa<\/jats:italic> for both radiotracers, and of the two, higher for <jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FPHCys than <jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FET. Blocking experiments with non-radioactive <jats:sc>d<\/jats:sc>-[<jats:sup>19<\/jats:sup>F]FPHCys confirmed specificity of uptake. <jats:italic>In vivo<\/jats:italic>, <jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FPHCys had greater accumulation in <jats:italic>S. aureus<\/jats:italic> infection compared with sterile inflammation, which was statistically significant. As anticipated, [<jats:sup>18<\/jats:sup>F]FDG showed no significant difference in uptake between infection and inflammation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p><jats:sc>d<\/jats:sc>-[<jats:sup>18<\/jats:sup>F]FPHCys uptake was higher in infected tissues than inflammation, and represents a fluorine-18 labelled <jats:sc>d<\/jats:sc>-AA with potential to detect a <jats:italic>S. aureus<\/jats:italic> reference strain (Xen29) <jats:italic>in vivo<\/jats:italic>. Additional studies are needed to evaluate uptake of this radiotracer in clinical isolates.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11307-024-01929-7","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T17:19:35Z","timestamp":1719595175000},"page":"704-713","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pilot Evaluation of S-(3-[18F]Fluoropropyl)-d-Homocysteine and O-(2-[18F]Fluoroethyl)-d-Tyrosine as Bacteria-Specific Radiotracers for PET Imaging of Infection"],"prefix":"10.1007","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-8731","authenticated-orcid":false,"given":"Helen M.","family":"Betts","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-7514","authenticated-orcid":false,"given":"Jeni C.","family":"Luckett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2250-1397","authenticated-orcid":false,"given":"Philip J.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"unstructured":"World Health Organisation\u00a0(n.d.) 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