Beschreibung:
<jats:p>The development of bacteria‐specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N‴‐tetraacetic acid (DOTA) conjugated peptide [<jats:sup>68</jats:sup>Ga]Ga‐DOTA‐K‐A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [<jats:sup>68</jats:sup>Ga]Ga‐DOTA‐K‐A9 synthesis omitting the use of acetone was developed, yielding 93 ± 0.9% radiochemical purity. The in vivo infection binding specificity of [<jats:sup>68</jats:sup>Ga]Ga‐DOTA‐K‐A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous <jats:styled-content style="fixed-case"><jats:italic>Staphylococcus aureus</jats:italic></jats:styled-content> infection or turpentine‐induced inflammation and compared with 2‐deoxy‐2‐[<jats:sup>18</jats:sup>F]fluoro‐<jats:italic>D</jats:italic>‐glucose ([<jats:sup>18</jats:sup>F]FDG). The scans showed that [<jats:sup>68</jats:sup>Ga]Ga‐DOTA‐K‐A9 accumulated in all the infected mice at injected doses ≥3.6 MBq. However, the tracer was not found to be selective towards infection, since the [<jats:sup>68</jats:sup>Ga]Ga‐DOTA‐K‐A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5‐carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA‐K‐A9, the microscopy results suggested that TAMRA‐K‐A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [<jats:sup>68</jats:sup>Ga]Ga‐DOTA‐K‐A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria.</jats:p>