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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 2/2015

01-02-2015 | Original Article

Targeted radionuclide therapy with RAFT-RGD radiolabelled with 90Y or 177Lu in a mouse model of αvβ3-expressing tumours

Authors: A. Bozon-Petitprin, S. Bacot, A. S. Gauchez, M. Ahmadi, J. C. Bourre, D. Marti-Batlle, P. Perret, A. Broisat, L. M. Riou, M. Claron, D. Boturyn, D. Fagret, Catherine Ghezzi, J. P. Vuillez

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2015

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Abstract

Purpose

The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β− emitters in a nude mouse model of αvβ3 integrin-expressing tumours.

Methods

Biodistribution and SPECT/CT imaging studies were performed after injection of 90Y-RAFT-RGD or 177Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with 90Y-RAFT-RGD or 177Lu-RAFT-RGD and 90Y-RAFT-RAD or 177Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment.

Results

Injection of 37 MBq of 90Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of 177Lu-RAFT-RGD into mice with small αvβ3-positive tumours 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 αvβ3-negative tumours.

Conclusion

90Y-RAFT-RGD and 177Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy.
Appendix
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Metadata
Title
Targeted radionuclide therapy with RAFT-RGD radiolabelled with 90Y or 177Lu in a mouse model of αvβ3-expressing tumours
Authors
A. Bozon-Petitprin
S. Bacot
A. S. Gauchez
M. Ahmadi
J. C. Bourre
D. Marti-Batlle
P. Perret
A. Broisat
L. M. Riou
M. Claron
D. Boturyn
D. Fagret
Catherine Ghezzi
J. P. Vuillez
Publication date
01-02-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2015
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-014-2891-7

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