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Assessment of gluca...
Assessment of glucagon receptor occupancy by Positron Emission Tomography in non-human primates
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- Eriksson, Olof (författare)
- Uppsala universitet,Institutionen för läkemedelskemi,Science for Life Laboratory, SciLifeLab,Antaros Med AB, Molndal, Sweden
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- Velikyan, Irina, 1966- (författare)
- Uppsala universitet,Institutionen för läkemedelskemi
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- Haack, T (författare)
- Sanofi Aventis, Frankfurt, Germany
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- Bossart, M (författare)
- Sanofi Aventis, Frankfurt, Germany
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- Evers, A (författare)
- Sanofi Aventis, Frankfurt, Germany
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- Laitinen, I (författare)
- Sanofi Aventis, Frankfurt, Germany
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- Larsen, PJ (författare)
- Sanofi Aventis, Frankfurt, Germany;Bayer Pharmaceut, Wuppertal, Germany
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- Plettenburg, O (författare)
- Sanofi Aventis, Frankfurt, Germany;German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Med Chem, Neuherberg, Germany;Leibniz Univ Hannover, Inst Organ Chem, Hannover, Germany
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- Takano, A (författare)
- Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden;Stockholm Cty Council, Stockholm, Sweden
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- Halldin, C (författare)
- Karolinska Institutet,Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden;Stockholm Cty Council, Stockholm, Sweden;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore
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- Antoni, Gunnar (författare)
- Uppsala universitet,Institutionen för läkemedelskemi
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- Johansson, L (författare)
- Antaros Med AB, Molndal, Sweden
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- Pierrou, S (författare)
- Antaros Med AB, Molndal, Sweden
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- Wagner, M (författare)
- Sanofi Aventis, Frankfurt, Germany
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(creator_code:org_t)
- 2019-10-18
- 2019
- Engelska.
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 14960-
- Relaterad länk:
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https://www.nature.c...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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http://kipublication...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Eriksson, Olof
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Velikyan, Irina, ...
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Haack, T
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Bossart, M
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Evers, A
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Laitinen, I
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Larsen, PJ
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Plettenburg, O
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Takano, A
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Halldin, C
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Antoni, Gunnar
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Johansson, L
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Pierrou, S
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Wagner, M
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- MEDICIN OCH HÄLSOVETENSKAP
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Scientific repor ...
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Karolinska Institutet
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Uppsala universitet