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In vivo imaging of tumour angiogenesis in mice with the αvβ3 integrin-targeted tracer 99mTc-RAFT-RGD

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

Abstract

Purpose

The molecular imaging of tumour neoangiogenesis currently represents a major field of research for the diagnostic and treatment strategy of solid tumours. Endothelial cells from tumour neovessels overexpress the αvβ3 integrin, which selectively binds to Arg-Gly-Asp (RGD)-containing peptides. We evaluated the potential of the novel radiotracer 99mTc-RAFT-RGD for the non-invasive molecular imaging of αvβ3 integrin expression in mice models of tumour development.

Methods

99mTc-RAFT-RGD, 99mTc-cRGD (specific control) and 99mTc-RAFT-RAD (non-specific control) were injected intravenously to mice bearing B16F0 or TS/A-pc tumours. In vivo whole-body tomographic imaging and post-mortem biodistribution studies were performed 60 min following tracer injection. Adjacent tumour slices were used to compare the localisation of neovessels from immunostaining and the pattern of 99mTc-RAFT-RGD uptake from autoradiographic ex vivo imaging.

Results

Biodistribution studies indicated that 99mTc-RAFT-RGD tumour uptake was significantly higher than that of 99mTc-RAFT-RAD in B16F0 (2.4±0.5 vs 1.0±0.1%ID/g, respectively) and in TS/A-pc tumours (2.7±0.8 vs 0.7±0.1%ID/g, respectively). Immunohistochemical and autoradiographic studies indicated that 99mTc-RAFT-RGD intratumoural uptake preferentially occurred in angiogenic areas. Tomographic imaging allowed tumour visualisation following injection of 99mTc-RAFT-RGD and 99mTc-cRGD with similar tumour-to-contralateral muscle (T/CM) ratios in B16F0 and in TS/A-pc tumours whereas 99mTc-RAFT-RAD T/CM ratios did not allow tumour imaging. In accordance with the higher level of αvβ3 integrin expression on TS/A-pc tumours than on B16F0 tumours as determined from western blot and immunoprecipitation analyses, the 99mTc-RAFT-RGD T/CM ratio was significantly higher in TS/A-pc than in B16F0 tumours.

Conclusion

99mTc-RAFT-RGD allowed the in vivo imaging of αvβ3 integrin tumour expression.

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Acknowledgements

All the experiments described in the present study were approved by the Animal Care and Use Committee of the Centre de Recherche et Service de Santé des Armées (CRSSA, La Tronche, France, Authorisation # 2004/25.0) and the experiments were performed by an authorised individual (L. Sancey, authorisation # 38 05 32). Financial support was provided by the National Institute for Health and Medical Research (INSERM), the Ligue Nationale Contre le Cancer (LNCC) and the Association pour la Recherche contre le Cancer (ARC).

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Authors and Affiliations

  1. INSERM, U877, Radiopharmaceutiques Biocliniques, La Tronche, France

    Lucie Sancey, Valérie Ardisson, Laurent M. Riou, Mitra Ahmadi, Danièle Marti-Batlle, Daniel Fagret, Catherine Ghezzi & Jean-Philippe Vuillez

  2. Université Joseph Fourier, Grenoble, France

    Lucie Sancey, Valérie Ardisson, Laurent M. Riou, Mitra Ahmadi, Danièle Marti-Batlle, Didier Boturyn, Pascal Dumy, Daniel Fagret, Catherine Ghezzi & Jean-Philippe Vuillez

  3. Département de Chimie Moléculaire, CNRS, UMR-5250, Grenoble, France

    Didier Boturyn & Pascal Dumy

  4. INSERM, U877, Radiopharmaceutiques Biocliniques, Faculté de Médecine, Université de Grenoble, 38700, La Tronche, France

    Laurent M. Riou

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  1. Lucie Sancey
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Correspondence to Laurent M. Riou.

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Sancey, L., Ardisson, V., Riou, L.M. et al. In vivo imaging of tumour angiogenesis in mice with the αvβ3 integrin-targeted tracer 99mTc-RAFT-RGD. Eur J Nucl Med Mol Imaging 34, 2037–2047 (2007). https://doi.org/10.1007/s00259-007-0497-z

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