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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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Acknowledgments

This work was partly funded by the French programme Investissement d’Avenir run by the Agence Nationale pour la Recherche’ (grant Infrastructure d’avenir en Biologie Santé - ANR-11-INBS-0006) and by the Agence Nationale pour la Recherche et la Technologie (ANRT).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. INSERM, U1039, Grenoble, 38000, France

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

  2. Université de Grenoble, UMR-S1039, Grenoble, 38000, France

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

  3. CHRU Grenoble, Hôpital Michallon, Service de Médecine Nucléaire, Grenoble, 38000, France

    A. S. Gauchez, J. C. Bourre, D. Fagret & J. P. Vuillez

  4. CNRS, UMR 5250, Département de Chimie Moléculaire, Grenoble, 38000, France

    M. Claron & D. Boturyn

  5. INSERM U1039, Radiopharmaceutiques biocliniques, Bâtiment Jean Roget, Domaine de la Merci, Faculté de Médecine, 38700, La Tronche, France

    Catherine Ghezzi

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  1. A. Bozon-Petitprin
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Corresponding author

Correspondence to Catherine Ghezzi.

Additional information

C. Ghezzi and J. P. Vuillez contributed equally to this work.

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Bozon-Petitprin, A., Bacot, S., Gauchez, A.S. et al. Targeted radionuclide therapy with RAFT-RGD radiolabelled with 90Y or 177Lu in a mouse model of αvβ3-expressing tumours. Eur J Nucl Med Mol Imaging 42, 252–263 (2015). https://doi.org/10.1007/s00259-014-2891-7

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  • DOI: https://doi.org/10.1007/s00259-014-2891-7

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