New Radiolabeled Exendin Analogues Show Reduced Renal Retention.
Mice
Animals
Exenatide
/ chemistry
Insulinoma
/ diagnosis
Positron Emission Tomography Computed Tomography
Gallium Radioisotopes
/ chemistry
Mice, Nude
Tissue Distribution
Isoleucine
/ metabolism
Positron-Emission Tomography
/ methods
Glucagon-Like Peptide-1 Receptor
/ metabolism
Pancreatic Neoplasms
/ drug therapy
Kidney
/ metabolism
Methionine
/ metabolism
Ga-68
Lu-177
PET/CT
exendin
insulinomas
renal retention
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
03 07 2023
03 07 2023
Historique:
medline:
4
7
2023
pubmed:
2
6
2023
entrez:
2
6
2023
Statut:
ppublish
Résumé
PET imaging of the glucagon-like peptide-1 receptor (GLP-1R) using radiolabeled exendin is a promising imaging method to detect insulinomas. However, high renal accumulation of radiolabeled exendin could hamper the detection of small insulinomas in proximity to the kidneys and limit its use as a radiotherapeutic agent. Here, we report two new exendin analogues for GLP-1R imaging and therapy, designed to reduce renal retention by incorporating a cleavable methionine-isoleucine (Met-Ile) linker. We examined the renal retention and insulinoma targeting properties of these new exendin analogues in a nude mouse model bearing subcutaneous GLP-1R-expressing insulinomas. NOTA or DOTA was conjugated via a methionine-isoleucine linker to the C-terminus of exendin-4 (NOTA-MI-exendin-4 or DOTA-MI-exendin-4). NOTA- and DOTA-exendin-4 without the linker were used as references. The affinity for GLP-1R was determined in a competitive binding assay using GLP-1R transfected cells. Biodistribution of [
Identifiants
pubmed: 37265006
doi: 10.1021/acs.molpharmaceut.3c00117
pmc: PMC10324399
doi:
Substances chimiques
Exenatide
9P1872D4OL
Gallium Radioisotopes
0
Isoleucine
04Y7590D77
Glucagon-Like Peptide-1 Receptor
0
Methionine
AE28F7PNPL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3519-3528Références
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