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

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

Authors :
Pascale Perret
Laurent Riou
A. Bozon-Petitprin
Daniel Fagret
Didier Boturyn
J.P. Vuillez
J.C. Bourre
M. Claron
Sandrine Bacot
Anne-Sophie Gauchez
Alexis Broisat
Catherine Ghezzi
Mitra Ahmadi
D. Marti-Batlle
Lardato, Marielle
Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID
Radiopharmaceutiques biocliniques (LRB)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Hôpital Michallon
Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM)
Département de Chimie Moléculaire (DCM)
Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
ANR-11-INBS-0006,FLI,France Life Imaging(2011)
Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF)
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS)
Centre National de la Recherche Scientifique (CNRS)-École Supérieure Chimie Physique Électronique de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon)
Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)
Université de Lyon
Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE)
Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Radiopharmaceutiques biocliniques
Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)
Source :
European Journal of Nuclear Medicine and Molecular Imaging, European Journal of Nuclear Medicine and Molecular Imaging, 2015, 42 (2), pp.252-263. ⟨10.1007/s00259-014-2891-7⟩, European Journal of Nuclear Medicine and Molecular Imaging, Springer Verlag (Germany), 2015, 42 (2), pp.252-263. ⟨10.1007/s00259-014-2891-7⟩
Publication Year :
2015
Publisher :
HAL CCSD, 2015.

Abstract

International audience; PurposeThe 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.MethodsBiodistribution 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.ResultsInjection 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.Conclusion90Y-RAFT-RGD and 177Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy.

Details

Language :
English
ISSN :
16197070 and 16197089
Database :
OpenAIRE
Journal :
European Journal of Nuclear Medicine and Molecular Imaging, European Journal of Nuclear Medicine and Molecular Imaging, 2015, 42 (2), pp.252-263. ⟨10.1007/s00259-014-2891-7⟩, European Journal of Nuclear Medicine and Molecular Imaging, Springer Verlag (Germany), 2015, 42 (2), pp.252-263. ⟨10.1007/s00259-014-2891-7⟩
Accession number :
edsair.doi.dedup.....2da339bdeba40064007421a30c6d016c
Full Text :
https://doi.org/10.1007/s00259-014-2891-7