Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 12359-12378 |
| Seitenumfang | 20 |
| Fachzeitschrift | Journal of medicinal chemistry |
| Jahrgang | 64 |
| Ausgabenummer | 16 |
| Frühes Online-Datum | 9 Aug. 2021 |
| Publikationsstatus | Veröffentlicht - 26 Aug. 2021 |
Abstract
The diagnosis of bacterial infections at deep body sites benefits from noninvasive imaging of molecular probes that can be traced by positron emission tomography (PET). We specifically labeled bacteria by targeting their iron transport system with artificial siderophores. The cyclen-based probes contain different binding sites for iron and the PET nuclide gallium-68. A panel of 11 siderophores with different iron coordination numbers and geometries was synthesized in up to 8 steps, and candidates with the best siderophore potential were selected by a growth recovery assay. The probes [68Ga]7 and [68Ga]15 were found to be suitable for PET imaging based on their radiochemical yield, radiochemical purity, and complex stability in vitro and in vivo. Both showed significant uptake in mice infected with Escherichia coli and were able to discern infection from lipopolysaccharide-triggered, sterile inflammation. The study qualifies cyclen-based artificial siderophores as readily accessible scaffolds for the in vivo imaging of bacteria.
ASJC Scopus Sachgebiete
- Biochemie, Genetik und Molekularbiologie (insg.)
- Molekularmedizin
- Pharmakologie, Toxikologie und Pharmazie (insg.)
- Wirkstoffforschung
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in: Journal of medicinal chemistry, Jahrgang 64, Nr. 16, 26.08.2021, S. 12359-12378.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Optimization of Artificial Siderophores as 68Ga-Complexed PET Tracers for in Vivo Imaging of Bacterial Infections
AU - Peukert, Carsten
AU - Langer, Laura N.B.
AU - Wegener, Sophie M.
AU - Tutov, Anna
AU - Bankstahl, Jens P.
AU - Karge, Bianka
AU - Bengel, Frank M.
AU - Ross, Tobias L.
AU - Brönstrup, Mark
N1 - Funding Information: The presented work was supported by a “Kekulé-Stipendium” of the “Fonds der chemischen Industrie (VCI)”, as well as with a grant from the Joint Programming Initiative on Antimicrobial Resistance (JPI AMR, grant number: 01KI1825).
PY - 2021/8/26
Y1 - 2021/8/26
N2 - The diagnosis of bacterial infections at deep body sites benefits from noninvasive imaging of molecular probes that can be traced by positron emission tomography (PET). We specifically labeled bacteria by targeting their iron transport system with artificial siderophores. The cyclen-based probes contain different binding sites for iron and the PET nuclide gallium-68. A panel of 11 siderophores with different iron coordination numbers and geometries was synthesized in up to 8 steps, and candidates with the best siderophore potential were selected by a growth recovery assay. The probes [68Ga]7 and [68Ga]15 were found to be suitable for PET imaging based on their radiochemical yield, radiochemical purity, and complex stability in vitro and in vivo. Both showed significant uptake in mice infected with Escherichia coli and were able to discern infection from lipopolysaccharide-triggered, sterile inflammation. The study qualifies cyclen-based artificial siderophores as readily accessible scaffolds for the in vivo imaging of bacteria.
AB - The diagnosis of bacterial infections at deep body sites benefits from noninvasive imaging of molecular probes that can be traced by positron emission tomography (PET). We specifically labeled bacteria by targeting their iron transport system with artificial siderophores. The cyclen-based probes contain different binding sites for iron and the PET nuclide gallium-68. A panel of 11 siderophores with different iron coordination numbers and geometries was synthesized in up to 8 steps, and candidates with the best siderophore potential were selected by a growth recovery assay. The probes [68Ga]7 and [68Ga]15 were found to be suitable for PET imaging based on their radiochemical yield, radiochemical purity, and complex stability in vitro and in vivo. Both showed significant uptake in mice infected with Escherichia coli and were able to discern infection from lipopolysaccharide-triggered, sterile inflammation. The study qualifies cyclen-based artificial siderophores as readily accessible scaffolds for the in vivo imaging of bacteria.
UR - http://www.scopus.com/inward/record.url?scp=85113840314&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.1c01054
DO - 10.1021/acs.jmedchem.1c01054
M3 - Article
C2 - 34370949
AN - SCOPUS:85113840314
VL - 64
SP - 12359
EP - 12378
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
SN - 0022-2623
IS - 16
ER -