Pre-clinical evaluation of eight DOTA coupled gastrin-releasing peptide receptor (GRP-R) ligands for in vivo targeting of receptor-expressing tumors

EJNMMI Research
Antonella AccardoLuigi Aloj

Abstract

Overexpression of the gastrin-releasing peptide receptor (GRP-R) has been documented in several human neoplasms such as breast, prostate, and ovarian cancer. There is growing interest in developing radiolabeled peptide-based ligands toward these receptors for the purpose of in vivo imaging and radionuclide therapy of GRP-R-overexpressing tumors. A number of different peptide sequences, isotopes, and labeling methods have been proposed for this purpose. The aim of this work is to perform a direct side-by-side comparison of different GRP-R binding peptides utilizing a single labeling strategy to identify the most suitable peptide sequence. Solid-phase synthesis of eight derivatives (BN1-8) designed based on literature analysis was carried out. Peptides were coupled to the DOTA chelator through a PEG4 spacer at the N-terminus. Derivatives were characterized for serum stability, binding affinity on PC-3 human prostate cancer cells, biodistribution in tumor-bearing mice, and gamma camera imaging at 1, 6, and 24 h after injection. Serum stability was quite variable among the different compounds with half-lives ranging from 16 to 400 min at 37 °C. All compounds tested showed K d values in the nanomolar range with the exception of BN3 ...Continue Reading

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Citations

Aug 3, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna Lucia TorneselloFranco Maria Buonaguro
Nov 20, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Paul HoppenzAnnette G Beck-Sickinger
Aug 28, 2020·Frontiers in Pharmacology·Karla de Castro Figueiredo BordonEliane Candiani Arantes
Jun 20, 2017·Journal of Peptide Science : an Official Publication of the European Peptide Society·Jean Martinez
May 20, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Brendan J EvansJoanne F Jamie
Feb 17, 2017·British Journal of Cancer·Onofrio Antonio CatalanoBruce Robert Rosen
Aug 26, 2018·Molecular Biology Reports·Syed Faheem Askari RizviRashid Rasheed
Apr 25, 2020·Bioorganic Chemistry·Fariba MalekiNourollah Sadeghzadeh
Oct 26, 2016·Bioorganic & Medicinal Chemistry·Anjuman Ara BegumIstvan Toth

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Methods Mentioned

BETA
saturation binding
xenografts
xenograft

Software Mentioned

Prism
GraphPad
LabScan

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