Targeted radionuclide therapy with RAFT-RGD radiolabelled with (90)Y or (177)Lu in a mouse model of αvß3-expressing tumours.
Eur J Nucl Med Mol Imaging
; 42(2): 252-63, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25164771
ABSTRACT
PURPOSE:
The αvß3 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 αvß3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with ß(-) emitters in a nude mouse model of αvß3 integrin-expressing tumours.METHODS:
Biodistribution and SPECT/CT imaging studies were performed after injection of (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvß3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD and (90)Y-RAFT-RAD or (177)Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvß3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvß3. Tumour volume doubling time was used to evaluate the efficacy of each treatment.RESULTS:
Injection of 37 MBq of (90)Y-RAFT-RGD into mice with large αvß3-positive tumours or 37 MBq of (177)Lu-RAFT-RGD into mice with small αvß3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of (90)Y-RAFT-RAD or 37 MBq of (177)Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of (90)Y-RAFT-RGD had no effect on the growth of αvß3-negative tumours.CONCLUSION:
(90)Y-RAFT-RGD and (177)Lu-RAFT-RGD are potent agents targeting αvß3-expressing tumours for internal targeted radiotherapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos Cíclicos
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Radioisótopos de Itrio
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Radiofármacos
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Integrina alfaVbeta3
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Lutecio
Límite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Nucl Med Mol Imaging
Asunto de la revista:
MEDICINA NUCLEAR
Año:
2015
Tipo del documento:
Article
País de afiliación:
Francia