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188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas

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

Abstract

Purpose

Lipid nanocapsules (LNC) entrapping lipophilic complexes of 188Re (188Re(S3CPh)2(S2CPh) [188Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intra-cerebral administration of 188Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model.

Methods

Female Fischer rats with 9L glioma were treated with a single injection of 188Re-SSS LNC by CED 6days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8 and 3Gy in comparison with blank LNC, perrhenate solution (4Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring 188Re elimination in faeces and urine over 72h after the CED injection. The therapeutic effect of 188Re-SSS LNC was assessed based on animal survival.

Results

CED of 188Re perrhenate solution resulted in rapid drug clearance with a brain T 1/2 of 7h. In contrast, when administered in LNC, 188Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72h. Rat median survival was significantly improved for the group treated with 8Gy 188Re-SSS LNC compared to the control group and blank LNC-treated animals. The increase in the median survival time was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8Gy proved to be a very effective dose, between toxic (10–12Gy) and ineffective (3–4Gy) doses.

Conclusions

These findings show that CED of 188Re-loaded LNC is a safe and potent anti-tumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of 188Re internal radiotherapy for the treatment of brain malignancy.

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Acknowledgements

The authors are very grateful to Sandrine Vinchon-Petit for CED experiences and to Myriam Moreau for her help in LNC formulation (INSERM U646, Angers, France) for her help in LNC formulation. We are also grateful to Pierre Legras and Jérome Roux (Service Commun d’Animalerie Hospitalo—Universitaire, Angers, France) for their technical assistance in animal experiments. This work was supported by a ‘Région des Pays de la Loire’ grant and by the county committee of Maine et Loire of ‘La ligue contre le cancer.’ Animal care was carried out in strict accordance to French Ministry of Agriculture regulations.

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Authors and Affiliations

  1. INSERM U646, Université d’Angers, Angers, 49100, France

    E. Allard, F. Hindre, C. Passirani, L. Lemaire, P. Menei & J-P. Benoit

  2. Département de Neurochirurgie, CHU d’Angers, Angers, 49033, France

    P. Menei

  3. UMR CNRS 6052, ENSCR, Rennes-Beaulieu, 35700, France

    N. Noiret

  4. Centre Eugène Marquis, Centre de médecine nucléaire, Rennes, 35700, France

    N. Lepareur

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  1. E. Allard
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  2. F. Hindre
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  3. C. Passirani
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  4. L. Lemaire
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  8. J-P. Benoit
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Correspondence to F. Hindre.

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Allard, E., Hindre, F., Passirani, C. et al. 188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas. Eur J Nucl Med Mol Imaging 35, 1838–1846 (2008). https://doi.org/10.1007/s00259-008-0735-z

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  • DOI: https://doi.org/10.1007/s00259-008-0735-z

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