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.
| Origine | Fichiers produits par l'(les) auteur(s) |
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| Origine | Fichiers produits par l'(les) auteur(s) |
|---|---|
| Licence |