دورية أكاديمية
Assessment of glucagon receptor occupancy by Positron Emission Tomography in non-human primates
| العنوان: | Assessment of glucagon receptor occupancy by Positron Emission Tomography in non-human primates |
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| المؤلفون: | Eriksson, Olof, Velikyan, Irina, Haack, Torsten, Bossart, Martin, Evers, Andreas, Laitinen, Iina, Larsen, Philip J., Plettenburg, Oliver, Takano, Akihiro, Halldin, Christer, Antoni, Gunnar, Johansson, Lars, Pierrou, Stefan, Wagner, Michael |
| بيانات النشر: | Uppsala universitet, Institutionen för läkemedelskemi Uppsala universitet, Science for Life Laboratory, SciLifeLab Antaros Med AB, Molndal, Sweden Sanofi Aventis, Frankfurt, Germany Sanofi Aventis, Frankfurt, Germany;Bayer Pharmaceut, Wuppertal, Germany 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 Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden;Stockholm Cty Council, Stockholm, Sweden 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 |
| سنة النشر: | 2019 |
| المجموعة: | Uppsala University: Publications (DiVA) |
| مصطلحات موضوعية: | Radiology, Nuclear Medicine and Medical Imaging, Radiologi och bildbehandling |
| الوصف: | 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 [Ga-68]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. [Ga-68]Ga-DO3A-S01-GCG was evaluated by dynamic PET in NHPs by a dose escalation study design, where up to 67 mu g/kg DO3A-S01-GCG peptide mass was co-injected. The test-retest reproducibility of [Ga-68]Ga-DO3A-S01-GCG binding in liver was evaluated. Furthermore, we investigated the effect of pre-treatment with acylated glucagon agonist 1-GCG on [Ga-68]GaDO3A-S01-GCG binding in liver. [Ga-68]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 mu g/kg. In vivo K-d for [Ga-68]Ga-DO3A-S01-GCG corresponded to 0.7 mu g/kg, which indicates high potency. The test-retest reproducibility for [Ga-68]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 [Ga-68]Ga-DO3A-S01-GCG PET examinations. In summary, PET radioligand [Ga-68]Ga-DO3A-S01-GCG is a quantitative biomarker of in vivo GCGR occupancy. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Scientific Reports, 2019, 9; orcid:0000-0002-2515-8790; orcid:0000-0002-1525-5255; http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-399094Test; PMID 31628379; ISI:000490988200019 |
| DOI: | 10.1038/s41598-019-51530-0 |
| الإتاحة: | https://doi.org/10.1038/s41598-019-51530-0Test http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-399094Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.60DD4B86 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-019-51530-0 |
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