ArticlePloS one2017
Radioiodinated Exendin-4 Is Superior to the Radiometal-Labelled Glucagon-Like Peptide-1 Receptor Probes Overcoming Their High Kidney Uptake.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Molecular imaging of neuroendocrine tumors: Current applications and future trends.Diagnostic and interventional imaging · 2025Review
- Automated radiofluorination of HER2 single domain antibody: the road towards the clinical translation of [EJNMMI radiopharmacy and chemistry · 2024Article
- Optimizing the Safety and Efficacy of Bio-Radiopharmaceuticals for Cancer Therapy.Pharmaceutics · 2023Article
- Peptide Radioligands in Cancer Theranostics: Agonists and Antagonists.Pharmaceuticals (Basel, Switzerland) · 2023Review
- RNA aptamers specific for transmembrane p24 trafficking protein 6 and Clusterin for the targeted delivery of imaging reagents and RNA therapeutics to human β cells.Nature communications · 2022Article
- The β Cell in Diabetes: Integrating Biomarkers With Functional Measures.Endocrine reviews · 2021Review
- Small peptide-based GLP-1R ligands: an approach to reduce the kidney uptake of radiolabeled GLP-1R-targeting agents?EJNMMI radiopharmacy and chemistry · 2021Article
- Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond.Frontiers in endocrinology · 2021Review
- Advances in GLP-1 receptor targeting radiolabeled agent development and prospective of theranostics.Theranostics · 2020Review
- Exendin-4 analogs in insulinoma theranostics.Journal of labelled compounds & radiopharmaceuticals · 2019Review
- Comparison of desferrioxamine and NODAGA for the gallium-68 labeling of exendin-4.EJNMMI radiopharmacy and chemistry · 2019Article
- Recent Topics Around Multiple Endocrine Neoplasia Type 1.The Journal of clinical endocrinology and metabolism · 2018Review
- Pancreatic imaging using an antibody fragment targeting the zinc transporter type 8: a direct comparison with radio-iodinated Exendin-4.Acta diabetologica · 2018Article
- The somatostatin receptor 2 antagonist 64Cu-NODAGA-JR11 outperforms 64Cu-DOTA-TATE in a mouse xenograft model.PloS one · 2018Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9-39) were studied in vitro using Ins-1E cells. Biodistribution and imaging studies were performed in nude mice bearing Ins-1E xenografts. In vitro evaluation demonstrated high affinity binding of the [Nle14,125I-Tyr40-NH2]Ex-4 agonist to the Ins-1E cells with fast internalization kinetics reaching a plateau after 30 min. The antagonist [Nle14,125I-Tyr40-NH2]Ex(9-39) did not internalize and had a 4-fold higher Kd value compared to the agonist. In contrast to [Nle14,125I-Tyr40-NH2]Ex(9-39), which showed low and transient tumor uptake, [Nle14,125I-Tyr40-NH2]Ex-4 demonstrated excellent in vivo binding properties with tumor uptake identical to that of 68Ga-Ex-4, but substantially lower kidney uptake resulting in a tumor-to-kidney ratio of 9.7 at 1 h compared to 0.3 with 68Ga-Ex-4. Accumulation of activity in thyroid and stomach for both peptides, which was effectively blocked by irenat, confirms that in vivo deiodination is the mechanism behind the low kidney retention of iodinated peptides. The 124I congener of [Nle14,125I-Tyr40-NH2]Ex-4 demonstrated a similar favourable biodistribution profile in the PET imaging studies in contrast to the typical biodistribution pattern of [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4. Our results demonstrate that iodinated Ex-4 is a very promising tracer for imaging of benign insulinomas. It solves the problem of high kidney uptake of the radiometal-labelled tracers by improving the tumor-to-kidney ratio measured for [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 by 32 fold.
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