Targeted radionuclide therapy with RAFT-RGD radiolabelled with 90Y or 177Lu in a mouse model of $\alpha$v$\beta$3-expressing tumours.
Purpose: The $\alpha$v$\beta$3 integrin plays an important role in tumor-induced angiogenesis, tumor proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the $\alpha$v$\beta$3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabeled with $\beta$- emitters in a nude mouse model of $\alpha$v$\beta$3 integrin-expressing tumors. Methods: Biodistribution and SPECT/CT imaging studies were performed after injection of 90Y-RAFT-RGD or 177Lu-RAFT-RGD in nude mice s.c. xenografted with $\alpha$v$\beta$3 integrin-expressing U-87 MG cells. Exptl. targeted radionuclide therapy with 90Y-RAFT-RGD or 177Lu-RAFT-RGD and 90Y-RAFT-RAD or 177Lu-RAFT-RAD (nonspecific controls) was evaluated by i.v. injection of the radionuclides into mice bearing $\alpha$v$\beta$3 integrin-expressing U-87 MG tumors of different sizes (small or large) or bearing TS/A-pc tumors that do not express $\alpha$v$\beta$3. Tumor vol. doubling time was used to evaluate the efficacy of each treatment. Results: Injection of 37 MBq of 90Y-RAFT-RGD into mice with large $\alpha$v$\beta$3-pos. tumors or 37 MBq of 177Lu-RAFT-RGD into mice with small $\alpha$v$\beta$3-pos. tumors caused significant growth delays compared to mice treated with 37 MBq of 90Y-RAFT-RAD or 37 MBq of 177Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of 90Y-RAFT-RGD had no effect on the growth of $\alpha$v$\beta$3-neg. tumors. Conclusion: 90Y-RAFT-RGD and 177Lu-RAFT-RGD are potent agents targeting $\alpha$v$\beta$3-expressing tumors for internal targeted radiotherapy. [on SciFinder(R)]
Références
- Titre
- Targeted radionuclide therapy with RAFT-RGD radiolabelled with 90Y or 177Lu in a mouse model of $\alpha$v$\beta$3-expressing tumours.
- Type de publication
- Article de revue
- Année de publication
- 2015
- Auteurs
- Bozon-Petitprin, A, Bacot S, Gauchez A S., Ahmadi M, Bourre J C., Marti-Batlle D, Perret P, Broisat A, Riou L M., Claron M, Boturyn Didier, Fagret D, Ghezzi Catherine, and Vuillez J P.
- Revue
- Eur. J. Nucl. Med. Mol. Imaging
- Volume
- 42
- Pagination
- 252–263
- ISSN
- 1619-7070
Soumis le 12 avril 2018