دورية أكاديمية
Imaging of the Glucose-Dependent Insulinotropic Polypeptide Receptor Using a Novel Radiolabeled Peptide Rationally Designed Based on Endogenous GIP and Synthetic Exendin-4 Sequences
| العنوان: | Imaging of the Glucose-Dependent Insulinotropic Polypeptide Receptor Using a Novel Radiolabeled Peptide Rationally Designed Based on Endogenous GIP and Synthetic Exendin-4 Sequences |
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| المؤلفون: | Velikyan, Irina, Bossart, Martin, Haack, Torsten, Laitinen, Iina, Estrada, Sergio, Johansson, Lars, Pierrou, Stefan, Wagner, Michael, Eriksson, Olof |
| بيانات النشر: | Uppsala universitet, Science for Life Laboratory, SciLifeLab Uppsala universitet, Translationell avbildning med PET Uppsala universitet, Plattformen för Preklinisk PET-MRI Uppsala Univ Hosp, PET Ctr, Ctr Med Imaging, SE-75185 Uppsala, Sweden. Sanofi, R&D Res Platform, Integrated Drug Discovery, D-65929 Frankfurt, Germany. Sanofi, Global Imaging, D-65929 Frankfurt, Germany.;Antaros Med AB, SE-75320 Uppsala, Sweden. Antaros Med AB, SE-43153 Mölndal, Sweden. |
| سنة النشر: | 2023 |
| المجموعة: | Uppsala University: Publications (DiVA) |
| مصطلحات موضوعية: | GIPR, PET, insulinoma, neuroendocrine tumors, Endocrinology and Diabetes, Endokrinologi och diabetes, Radiology, Nuclear Medicine and Medical Imaging, Radiologi och bildbehandling |
| الوصف: | Imaging and radiotherapy targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) could potentially benefit the management of neuroendocrine neoplasms (NENs), complementing clinically established radiopharmaceuticals. The aim of this study was to evaluate a GIPR-targeting positron emission tomography (PET) radioligand with receptor-specific binding, fast blood clearance, and low liver background uptake. The peptide DOTA-bioconjugate, C803-GIP, was developed based on the sequence of the endogenous GIP(1-30) and synthetic exendin-4 peptides with selective amino acid mutations to combine their specificity for the GIPR and in vivo stability, respectively. The Ga-68-labeled bioconjugate was evaluated in vitro in terms of binding affinity, specificity, and internalization in HEK293 cells transfected with the human GIPR, GLP1, or GCG receptors and in sections of human insulinoma and NENs. In vivo binding specificity, biodistribution, and tissue background were investigated in mice bearing huGIPR-HEK293 xenografts and in a pig. Ex vivo organ distribution, pharmacokinetics, and dosimetry were studied in normal rats. [Ga-68]Ga-C803-GIP was stable and demonstrated a high affinity to the huGIPR-HEK293 cells. Binding specificity was demonstrated in vitro in frozen sections of NENs and huGIPR-HEK293 cells. No specific uptake was observed in the negative controls of huGLP1R and huGCGR cells. A novel rationally designed PET radioligand, [Ga-68]Ga-C803-GIP, demonstrated promising binding characteristics and specificity towards the GIPR. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Pharmaceuticals, 2023, 16:1; orcid:0000-0002-3732-8857; orcid:0000-0002-8388-4619; orcid:0000-0002-2515-8790; http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-496581Test; PMID 36678558; ISI:000918744200001 |
| DOI: | 10.3390/ph16010061 |
| الإتاحة: | https://doi.org/10.3390/ph16010061Test http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-496581Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.4A016C4D |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ph16010061 |
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