Gadolinium-Based Nanoparticles AGuIX and Radiation Therapy for Multiple Brain Melanoma Metastases and Brain Tumors: From Bench to Bedside - Institut Lumière Matière Accéder directement au contenu
Communication Dans Un Congrès Année : 2016

Gadolinium-Based Nanoparticles AGuIX and Radiation Therapy for Multiple Brain Melanoma Metastases and Brain Tumors: From Bench to Bedside

Résumé

More than half of all clinical cancer patients undergo radiation therapy. Besides the poor prognosis for multiple brain metastases and brain tumors, the delivery of curative radiation dose to eradicate tumor is strongly restricted by the healthy proximal brain. We describe a nanoparticle which can act as MR contrast agent and radiosensitizer concomitantly, for the detection, monitoring and treatment of brain cancers. Biodistribution, toxicity and pharmacokinetic studies were carried out in rodents and cynomolgus monkeys to demonstrate the safety of the nanoparticles after intravenous injection. The MR imaging properties of the nanoparticles were used to monitor their tumor accumulation in rodent bearing brain tumors. In vitro and in vivo efficacy of the nanoparticles was evaluated in rodent bearing brain tumors. The regulatory toxicity investigations demonstrated the absence of any ante- or post-mortem finding in rodent and nonhuman primates after repeated administration of nanoparticles; thus, the no-observed-effect level (NOEL) was determined and a human equivalent dose of 120 mg/kg was defined. In rodents, MR imaging indicated the renal elimination of the nanoparticles and their passive accumulation in the tumor region for several hours. The combination of nanoparticles and irradiation created significant dose enhancement in vitro, and improved the survival of rodent bearing aggressive brain tumor. The therapeutic efficacy of AGuIX has been demonstrated in aggressive pathologies, i.e. multiple brain metastases and brain tumors. In addition, the nanoparticles possess natural T1-MRI contrast agent properties, conferring a dual-property for image-guided radiation therapy. The data in rodents and nonhuman primates clearly demonstrates and justifies their clinical translational potential. The upcoming first-in-man clinical trial will investigated both imaging and radiation therapy improvement for advanced precision medicine.
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Dates et versions

hal-01297642 , version 1 (04-04-2016)

Identifiants

  • HAL Id : hal-01297642 , version 1

Citer

Lucie Sancey, Shady Kotb, Sandrine Dufort, François Lux, Camille Verry, et al.. Gadolinium-Based Nanoparticles AGuIX and Radiation Therapy for Multiple Brain Melanoma Metastases and Brain Tumors: From Bench to Bedside. Forum de la recherche en cancérologie Rhône-Alpes Auvergne, Mar 2016, Lyon, France. ⟨hal-01297642⟩
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