Preclinical evaluation of potential infection-imaging probe [68Ga]Ga-DOTA-K-A9 in sterile and infectious inflammation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Preclinical evaluation of potential infection-imaging probe [68Ga]Ga-DOTA-K-A9 in sterile and infectious inflammation. / Nielsen, Karin M.; Jørgensen, Nis P.; Kyneb, Majbritt H.; Borghammer, Per; Meyer, Rikke L.; Thomsen, Trine R.; Bender, Dirk; Jensen, Svend B.; Nielsen, Ole L.; Alstrup, Aage K.O.
I: Journal of Labelled Compounds and Radiopharmaceuticals, Bind 61, Nr. 10, 2018, s. 780-795.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Preclinical evaluation of potential infection-imaging probe [68Ga]Ga-DOTA-K-A9 in sterile and infectious inflammation
AU - Nielsen, Karin M.
AU - Jørgensen, Nis P.
AU - Kyneb, Majbritt H.
AU - Borghammer, Per
AU - Meyer, Rikke L.
AU - Thomsen, Trine R.
AU - Bender, Dirk
AU - Jensen, Svend B.
AU - Nielsen, Ole L.
AU - Alstrup, Aage K.O.
PY - 2018
Y1 - 2018
N2 - 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 [68Ga]Ga-DOTA-K-A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [68Ga]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 [68Ga]Ga-DOTA-K-A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine-induced inflammation and compared with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). The scans showed that [68Ga]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 [68Ga]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 [68Ga]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.
AB - 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 [68Ga]Ga-DOTA-K-A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [68Ga]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 [68Ga]Ga-DOTA-K-A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine-induced inflammation and compared with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). The scans showed that [68Ga]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 [68Ga]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 [68Ga]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.
KW - bacterial infection
KW - fluorescence
KW - gallium-68
KW - murine models
KW - PET
KW - S aureus
KW - [Ga]Ga-DOTA-K-A9
U2 - 10.1002/jlcr.3640
DO - 10.1002/jlcr.3640
M3 - Journal article
C2 - 29790580
AN - SCOPUS:85051436957
VL - 61
SP - 780
EP - 795
JO - Journal of Labelled Compounds and Radiopharmaceuticals
JF - Journal of Labelled Compounds and Radiopharmaceuticals
SN - 0362-4803
IS - 10
ER -
ID: 201908435