Article Dans Une Revue Inorganic Chemistry Année : 2025

Advanced 64 Cu/67 Cu-Based Theranostics: Application of the Copper Chelator TE1PA to a Murine Model of HER2-positive Gastric Cancer

Résumé

The development of 64 Cu/67 Cu-based theranostic probes addresses the need for integrated cancer diagnosis and therapy. To target HER2-positive gastric cancer, trastuzumab was conjugated to p-SCN-Bn-TE1PA (DOL of 1.1-2.0), achieving high yields and purity. Binding assays on BT-474 cells confirmed the preserved cellular uptake of the bioconjugate. The successful radiolabeling of Trastuzumab-p-SCN-Bn-TE1PA (DOL of 2) with both the 64 Cu-and 67 Cu-isotopes demonstrated suitability for in vivo studies. In a preclinical model of HER2-positive gastric cancer, [ 64 Cu]Cu-Trastuzumab-p-SCN-Bn-TE1PA enabled effective PET imaging with tumor-specific uptake (21%IA/g) and clearance through the spleen, liver and kidneys. Therapeutic studies with [ 67 Cu]Cu Trastuzumab-p-SCN-BnTE1PA (10-20 MBq) demonstrated dose-dependent tumor inhibition of growth, without toxicity or adverse health effects. This work exemplifies the clinical potential of associating 64 Cu-imaging and 67 Cu-therapy. By combining a robust isotopic pair, a customized bifunctional chelator and trastuzumab, this study demonstrates a promising approach for HER2positive gastric cancer treatment in nuclear medicine, paving the way for personalized copper-based theranostics.

Fichier principal
Vignette du fichier
Advanced 64Cu67Cu-Based Theranostics, Tripier2025.pdf (908.72 Ko) Télécharger le fichier
SuppInfo_Advanced 64Cu67Cu-Based Theranostics, Tripier2025.pdf (2.9 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)
Licence
Origine Fichiers produits par l'(les) auteur(s)
Licence

Dates et versions

hal-05115478 , version 1 (16-06-2025)

Licence

Identifiants

Citer

Julie Pineau, Cédric Ollier, Céline Mothes, Sarah Belderbos, Nathalie Le Bris, et al.. Advanced 64 Cu/67 Cu-Based Theranostics: Application of the Copper Chelator TE1PA to a Murine Model of HER2-positive Gastric Cancer. Inorganic Chemistry, 2025, ⟨10.1021/acs.inorgchem.5c01513⟩. ⟨hal-05115478⟩
100 Consultations
72 Téléchargements

Altmetric

Partager

  • More