Tumor eradication in rat glioma and bypass of immunosuppressive barriers using internal radiation with 188Re-lipid nanocapsules

Vanpouille-Box, Claire; Lacoeuille, Franck; Belloche, Camille; Lepareur, Nicolas; Lemaire, Laurent; Lejeune, Jean; Benoı̂t, Jean-Pierre; Menei, Philippe; Couturier, O.; Garcion, Emmanuel; Hindré, François

doi:10.1016/j.biomaterials.2011.05.067

Cited by 64 publications

(54 citation statements)

References 48 publications

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“…As mentioned in Introduction, the radioactivity gradient created by locoregional administration of 188 Re-LNC showed to be the major determinant for an efficient treatment of rat glioma [18]. In the present study, the fact that we can now focus the radioactive material on α v β 3 expressing cells will also affect the resulting gradient of activity.…”

Section: In Vivo Biodistributionmentioning

confidence: 61%

“…Their size can be tuned within the range of 20-100 nm [9]. LNC have been used for the delivery of cancer therapeutics [10][11][12][13] and other drug molecules [14], macromolecules such as siRNA and DNA [15], and radiotherapeutics [16][17][18]. In the context of radiotherapy, 188 Re-LNC have been tested for locoregional treatment of glioma in rats by stereotactic administration [18].…”

Section: Introductionmentioning

confidence: 99%

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Tumour targeting of lipid nanocapsules grafted with cRGD peptides

Hirsjärvi

Belloche

Hindré

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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Combining targeting to therapy remains a major challenge in cancer treatment. To address this subject, the surface of lipid nanocapsules (LNC) were modified by grafting cRGD peptides, which are known to be recognised by α v β 3 integrins expressed by tumour endothelium and cancer cells. Applicability of this LNC-cRGD in tumour targeting was first assessed in vitro by the use of U87MG glioma cells. Biodistribution and tumour accumulation of radiolabelled LNC-cRGD in vivo were then evaluated in mice bearing the same subcutaneous xenograft. Flow cytometry and confocal microscopy results revealed that the cRGD grafting improved binding and internalization compared to negative control LNCcRAD and blank LNC. The peptide-grafted LNC remained in the blood circulation up to 3 hours with reduced capture by the RES organs. Tumour accumulation of LNC-cRGD with respect to LNC-cRAD was significantly higher at 1-3 hours. These results show that cRGD grafted to LNC has created a promising tumour-targetable nanocarrier that could be used in cancer treatment.

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Section: In Vivo Biodistributionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Tumour targeting of lipid nanocapsules grafted with cRGD peptides

Hirsjärvi

Belloche

Hindré

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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“…8 In recent years, radiolabeled nanoparticles such as 188 Re-lipid nanoparticles and 186 Re-liposome nanoparticles have been introduced for treatment of GBM via convection-enhanced delivery technique. [9][10][11][12] These studies demonstrated that the survival of tumor-bearing rats was significantly prolonged with therapeutic radiopharmaceutical treatment. Although the convection-enhanced delivery technique affords apparent benefits for GBM treatment, it might still cause certain drawbacks in clinical practice.…”

Section: Introductionmentioning

confidence: 97%

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

Huang

Lee

Chang

et al. 2015

IJN

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Purpose In this study, the 188 Re-labeled PEGylated nanoliposome ( 188 Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. Materials and methods The reporter cell line, F98 luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188 Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188 Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188 Re-liposome-treated rats. Results By using bioluminescent imaging, the well-established reporter cell line (F98 luc ) showed a high relationship between cell number and its bioluminescent intensity ( R 2 =0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188 Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188 Re-liposome-treated group than the control group ( P <0.05). As a result, the lifespan of glioma-bearing rats treated with 188 Re-liposome was prolonged 10.67% compared to the control group. Conclusion The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting 188 Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma-bearing rats while maintaining reasonable systemic radiation safety. Therefore, 188 Re-liposome could be a potential therapeutic agent for glioblastoma multiforme treatment.

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“…Furthermore, with new irradiation technologies it is possible to specifically target the tumor site and limit the irradiation of healthy surrounding tissue. Those procedures include stereotactic radiosurgery [g-rays produced from the decay of cobalt 60 (g-knife) or X-rays from a linear accelerator (Cyberknife1, Novalis1)] [9], hadrontherapy which uses heavy particles (protons or ions) presenting a ballistic advantage (Bragg Peak) [10], and brachytherapy for which the radiation source is placed in the close vicinity of the area requiring treatment [11,12].Finally, the therapeutic arsenal of GBM relies also on chemotherapy with the alkylating agent TMZ, conferring a Feature Review 0165-6147/ ß …”

mentioning

confidence: 99%