dc.identifier.uri |
http://dx.doi.org/10.15488/9828 |
|
dc.identifier.uri |
https://www.repo.uni-hannover.de/handle/123456789/9885 |
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dc.contributor.author |
Velikyan, Irina
|
|
dc.contributor.author |
Haack, Torsten
|
|
dc.contributor.author |
Bossart, Martin
|
|
dc.contributor.author |
Evers, Andreas
|
|
dc.contributor.author |
Laitinen, Ilina
|
|
dc.contributor.author |
Larsen, Philip
|
|
dc.contributor.author |
Plettenburg, Oliver
|
|
dc.contributor.author |
Johansson, Lars
|
|
dc.contributor.author |
Pierrou, Stefan
|
|
dc.contributor.author |
Wagner, Michael
|
|
dc.contributor.author |
Eriksson, Olof
|
|
dc.date.accessioned |
2020-05-18T09:16:28Z |
|
dc.date.available |
2020-05-18T09:16:28Z |
|
dc.date.issued |
2019 |
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dc.identifier.citation |
Velikyan, I.; Haack, T.; Bossart, M.; Evers, A.; Laitinen, I. et al.: First-in-class positron emission tomography tracer for the glucagon receptor. In: EJNMMI Research 9 (2019), 17. DOI: https://doi.org/10.1186/s13550-019-0482-0 |
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dc.description.abstract |
Abstract: The glucagon receptor (GCGR) is emerging as an important target in anti-diabetic therapy, especially as part of the pharmacology of dual glucagon-like peptide-1/glucagon (GLP-1/GCG) receptor agonists. However, currently, there are no suitable biomarkers that reliably demonstrate GCG receptor target engagement. Methods: Two potent GCG receptor peptide agonists, S01-GCG and S02-GCG, were labeled with positron emission tomography (PET) radionuclide gallium-68. The GCG receptor binding affinity and specificity of the resulting radiopharmaceuticals [ 68 Ga]Ga-DO3A-S01-GCG and [ 68 Ga]Ga-DO3A-S02-GCG were evaluated in HEK-293 cells overexpressing the human GCG receptor and on frozen hepatic sections from human, non-human primate, and rat. In in vivo biodistribution, binding specificity and dosimetry were assessed in rat. Results: [ 68 Ga]Ga-DO3A-S01-GCG in particular demonstrated GCG receptor-mediated binding in cells and liver tissue with affinity in the nanomolar range required for imaging. [ 68 Ga]Ga-DO3A-S01-GCG binding was not blocked by co-incubation of a GLP-1 agonist. In vivo binding in rat liver was GCG receptor specific with low non-specific binding throughout the body. Moreover, the extrapolated human effective doses, predicted from rat biodistribution data, allow for repeated PET imaging potentially also in combination with GLP-1R radiopharmaceuticals. Conclusion: [ 68 Ga]Ga-DO3A-S01-GCG thus constitutes a first-in-class PET tracer targeting the GCG receptor, with suitable properties for clinical development. This tool has potential to provide direct quantitative evidence of GCG receptor occupancy in humans. |
eng |
dc.language.iso |
eng |
|
dc.publisher |
Heidelberg : Springer Verlag |
|
dc.relation.ispartofseries |
EJNMMI Research 9 (2019) |
|
dc.rights |
CC BY 4.0 Unported |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Dual agonist |
eng |
dc.subject |
GCG |
eng |
dc.subject |
GLP-1 receptor |
eng |
dc.subject |
Glucagon |
eng |
dc.subject |
Type 2 diabetes |
eng |
dc.subject |
antidiabetic agent |
eng |
dc.subject |
cysteine |
eng |
dc.subject |
exendin 4 |
eng |
dc.subject |
Ga DO3A S01 GCG |
eng |
dc.subject |
Ga DO3A S02 GCG |
eng |
dc.subject |
gadoteridol |
eng |
dc.subject |
gallium 68 |
eng |
dc.subject |
glucagon like peptide 1 |
eng |
dc.subject |
glucagon like peptide 1 receptor agonist |
eng |
dc.subject |
glucagon receptor |
eng |
dc.subject |
glucagon receptor agonist |
eng |
dc.subject |
peptide |
eng |
dc.subject |
phosphorus |
eng |
dc.subject |
radioisotope |
eng |
dc.subject |
radiopharmaceutical agent |
eng |
dc.subject |
tracer |
eng |
dc.subject |
unclassified drug |
eng |
dc.subject |
adult |
eng |
dc.subject |
animal model |
eng |
dc.subject |
autoradiography |
eng |
dc.subject |
binding affinity |
eng |
dc.subject |
body weight |
eng |
dc.subject |
body weight loss |
eng |
dc.subject |
cAMP assay |
eng |
dc.subject |
carboxy terminal sequence |
eng |
dc.subject |
controlled study |
eng |
dc.subject |
dosimetry |
eng |
dc.subject |
effective dose (radiation) |
eng |
dc.subject |
female |
eng |
dc.subject |
gene overexpression |
eng |
dc.subject |
HEK293 cell line |
eng |
dc.subject |
high performance liquid chromatography |
eng |
dc.subject |
human |
eng |
dc.subject |
human cell |
eng |
dc.subject |
human tissue |
eng |
dc.subject |
internalization |
eng |
dc.subject |
isotope labeling |
eng |
dc.subject |
liver biopsy |
eng |
dc.subject |
liver tissue |
eng |
dc.subject |
male |
eng |
dc.subject |
nonhuman |
eng |
dc.subject |
positron emission tomography |
eng |
dc.subject |
priority journal |
eng |
dc.subject |
quality control |
eng |
dc.subject |
radioactivity |
eng |
dc.subject |
radiochemistry |
eng |
dc.subject |
rat |
eng |
dc.subject |
receptor affinity |
eng |
dc.subject |
receptor occupancy |
eng |
dc.subject |
retention time |
eng |
dc.subject.ddc |
610 | Medizin, Gesundheit
|
ger |
dc.title |
First-in-class positron emission tomography tracer for the glucagon receptor |
eng |
dc.type |
Article |
|
dc.type |
Text |
|
dc.relation.issn |
2191-219X |
|
dc.relation.doi |
https://doi.org/10.1186/s13550-019-0482-0 |
|
dc.bibliographicCitation.volume |
9 |
|
dc.bibliographicCitation.firstPage |
17 |
|
dc.description.version |
publishedVersion |
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tib.accessRights |
frei zug�nglich |
|