dc.identifier.uri |
http://dx.doi.org/10.15488/10490 |
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dc.identifier.uri |
https://www.repo.uni-hannover.de/handle/123456789/10567 |
|
dc.contributor.author |
Eriksson, Olof
|
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dc.contributor.author |
Velikyan, Irina
|
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dc.contributor.author |
Haack, Torsten
|
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dc.contributor.author |
Bossart, Martin
|
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dc.contributor.author |
Evers, Andreas
|
|
dc.contributor.author |
Laitinen, Iina
|
|
dc.contributor.author |
Larsen, Philip J.
|
|
dc.contributor.author |
Plettenburg, Oliver
|
|
dc.contributor.author |
Takano, Akihiro
|
|
dc.contributor.author |
Halldin, Christer
|
|
dc.contributor.author |
Antoni, Gunnar
|
|
dc.contributor.author |
Johansson, Lars
|
|
dc.contributor.author |
Pierrou, Stefan
|
|
dc.contributor.author |
Wagner, Michael
|
|
dc.date.accessioned |
2021-03-09T09:50:54Z |
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dc.date.available |
2021-03-09T09:50:54Z |
|
dc.date.issued |
2019 |
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dc.identifier.citation |
Eriksson, O.; Velikyan, I.; Haack, T.; Bossart, M.; Evers, A. et al.: Assessment of glucagon receptor occupancy by Positron Emission Tomography in non-human primates. In: Scientific Reports 9 (2019), Nr. 1, 14960. DOI: https://doi.org/10.1038/s41598-019-51530-0 |
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dc.description.abstract |
The glucagon receptor (GCGR) is an emerging target in anti-diabetic therapy. Reliable biomarkers for in vivo activity on the GCGR, in the setting of dual glucagon-like peptide 1/glucagon (GLP-1/GCG) receptor agonism, are currently unavailable. Here, we investigated [68Ga]Ga-DO3A-S01-GCG as a biomarker for GCGR occupancy in liver, the tissue with highest GCGR expression, in non-human primates (NHP) by PET. [68Ga]Ga-DO3A-S01-GCG was evaluated by dynamic PET in NHPs by a dose escalation study design, where up to 67 µg/kg DO3A-S01-GCG peptide mass was co-injected. The test-retest reproducibility of [68Ga]Ga-DO3A-S01-GCG binding in liver was evaluated. Furthermore, we investigated the effect of pre-treatment with acylated glucagon agonist 1-GCG on [68Ga]Ga-DO3A-S01-GCG binding in liver. [68Ga]Ga-DO3A-S01-GCG bound to liver in vivo in a dose-dependent manner. Negligible peptide mass effect was observed for DO3A-S01-GCG doses <0.2 µg/kg. In vivo Kd for [68Ga]Ga-DO3A-S01-GCG corresponded to 0.7 µg/kg, which indicates high potency. The test-retest reproducibility for [68Ga]Ga-DO3A-S01-GCG binding in liver was 5.7 ± 7.9%. Pre-treatment with 1-GCG, an acylated glucagon agonist, resulted in a GCGR occupancy of 61.5 ± 9.1% in liver. Predicted human radiation dosimetry would allow for repeated annual [68Ga]Ga-DO3A-S01-GCG PET examinations. In summary, PET radioligand [68Ga]Ga-DO3A-S01-GCG is a quantitative biomarker of in vivo GCGR occupancy. © 2019, The Author(s). |
eng |
dc.language.iso |
eng |
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dc.publisher |
London : Nature Publishing Group |
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dc.relation.ispartofseries |
Scientific Reports 9 (2019), Nr. 1 |
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dc.rights |
CC BY 4.0 Unported |
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dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
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dc.subject |
glucagon receptor |
eng |
dc.subject |
GCGR |
eng |
dc.subject |
biomarker |
eng |
dc.subject |
liver |
eng |
dc.subject.ddc |
500 | Naturwissenschaften
|
ger |
dc.subject.ddc |
600 | Technik
|
ger |
dc.title |
Assessment of glucagon receptor occupancy by Positron Emission Tomography in non-human primates |
|
dc.type |
Article |
|
dc.type |
Text |
|
dc.relation.essn |
2045-2322 |
|
dc.relation.doi |
https://doi.org/10.1038/s41598-019-51530-0 |
|
dc.bibliographicCitation.issue |
1 |
|
dc.bibliographicCitation.volume |
9 |
|
dc.bibliographicCitation.firstPage |
14960 |
|
dc.description.version |
publishedVersion |
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tib.accessRights |
frei zug�nglich |
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