| Autor: |
Akter A; Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King's College London, London SE1 9NH, United Kingdom., Firth G; School of Biomedical Engineering and Imaging Sciences, Faculty of Life Science and Medicine, King's College London, London SE1 7EH, United Kingdom., Darwesh AMF; School of Biomedical Engineering and Imaging Sciences, Faculty of Life Science and Medicine, King's College London, London SE1 7EH, United Kingdom.; Department of Radiologic Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Cooper MS; School of Biomedical Engineering and Imaging Sciences, Faculty of Life Science and Medicine, King's College London, London SE1 7EH, United Kingdom., Chuljerm H; Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King's College London, London SE1 9NH, United Kingdom.; School of Health Sciences Research, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai 50200, Thailand., Cilibrizzi A; Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King's College London, London SE1 9NH, United Kingdom., Blower PJ; School of Biomedical Engineering and Imaging Sciences, Faculty of Life Science and Medicine, King's College London, London SE1 7EH, United Kingdom., Hider RC; Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King's College London, London SE1 9NH, United Kingdom., Lyons O; Department of Surgery, University of Otago, Christchurch 8013, New Zealand., Schelenz S; Department of Microbiology, Kings College Hospital NHS Foundation Trust, London SE5 9RS, United Kingdom., Mehra V; Department of Hematology, King's College Hospital NHS Foundation Trust, London SE5 9RS, United Kingdom., Abbate V; Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King's College London, London SE1 9NH, United Kingdom. |
| Abstrakt: |
Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([ 68 Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. In vitro uptake of [ 68 Ga]Ga-SKN by Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , and S. epidermidis , but no uptake by Candida glabrata , C. albicans , or Aspergillus fumigatus , demonstrated its specificity to bacterial species. Whole-body [ 68 Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent ex vivo biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [ 68 Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging. |
