Dépôt numérique

Novel dimeric DOTA-coupled peptidic Y1-receptor antagonists for targeting of neuropeptide Y receptor-expressing cancers


Téléchargements par mois depuis la dernière année

Plus de statistiques...

Chatenet, David ORCID logoORCID: https://orcid.org/0000-0002-7270-4328; Cescato, Renzo; Waser, Beatrice; Erchegyi, Judit; Rivier, Jean E. et Reubi, Jean Claude (2011). Novel dimeric DOTA-coupled peptidic Y1-receptor antagonists for targeting of neuropeptide Y receptor-expressing cancers EJNMMI research , vol. 1 , nº 1. p. 21. DOI: 10.1186/2191-219X-1-21.

[thumbnail of Novel dimeric DOTA-coupled peptidic.pdf]
PDF - Version publiée
Disponible sous licence Creative Commons Attribution.

Télécharger (468kB) | Prévisualisation



Several peptide hormone receptors were identified that are specifically over-expressed on the cell surface of certain human tumors. For example, high incidence and density of the Y1 subtype of neuropeptide Y (NPY) receptors are found in breast tumors. Recently, we demonstrated that the use of potent radiolabeled somatostatin or bombesin receptor antagonists considerably improved the sensitivity of in vivo imaging when compared to agonists. We report here on the first DOTA-coupled peptidic Y1 receptor affine dimer antagonists.


Based on a Y1 affine dimeric peptide scaffold previously reported to competitively antagonize NPY-mediated processes, we have developed new dimeric DOTA-coupled Y1 receptor affine antagonists for scintigraphy and radiotherapy. These dimeric peptides were tested for their specific binding to Y1 expressed in SK-N-MC cells and Y2 expressed in SH-SY5Y as well as for their ability to mediate cAMP production in SK-N-MC cells.


Introduction of two DOTA moieties at the N-termini of the dimeric NPY analogs as well as the double Asn29 replacement by Dpr(DOTA) or Lys(DOTA) (6 and 10) moiety dramatically reduced binding affinity. However, asymmetric introduction of the DOTA moiety in one segment of the peptidic heterodimer (8 and 11) resulted in suitable antagonists for receptor targeting with high binding affinity for Y1. All compounds were devoid of Y2 binding affinity.


The design and the in vitro characterization of the first DOTA-coupled dimeric NPY receptor antagonist with high affinity and selectivity for Y1 over Y2 are described. This compound may be an excellent candidate for the imaging of Y1-positive tumors and their treatment.

Type de document: Article
Mots-clés libres: neuropeptide Y receptor; tumor imaging; oncology; peptide receptor radionuclide therapy; breast cancer; antagonist
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 09 mars 2024 22:37
Dernière modification: 09 mars 2024 22:37
URI: https://espace.inrs.ca/id/eprint/14486

Gestion Actions (Identification requise)

Modifier la notice Modifier la notice