Amide-to-triazole switch vs. in vivo NEP-inhibition approaches to promote radiopeptide targeting of GRPR-positive tumors.
Fiche publication
Date publication
septembre 2017
Journal
Nuclear medicine and biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VALVERDE Ibai
Tous les auteurs :
Maina T, Kaloudi A, Valverde IE, Mindt TL, Nock BA
Lien Pubmed
Résumé
Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG-[Nle]BBN(7-14) (1) was reported to improve the in vitro stability of resulting Lu-radioligands. On the other hand, in-situ inhibition of neutral endopeptidase (NEP) by coinjection of phosphoramidon (PA) was shown to significantly improve the in vivo stability and tumor uptake of biodegradable radiopeptides. We herein compare the impact of the two methods on the bioavailability and localization of Lu-DOTA-PEG-[Nle]BBN(7-14) analogs in GRPR-positive tumors in mice.
Mots clés
(177)Lu-bombesin, GRPR-radioligand, NEP-inhibition, Triazolyl-bombesin, Tumor targeting
Référence
Nucl. Med. Biol.. 2017 Sep;52:57-62