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Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment.

Le Duc G, Roux S, Paruta-Tuarez A, Dufort S, Brauer E, Marais A, Truillet C, Sancey L, Perriat P, Lux F, Tillement O - Cancer Nanotechnol (2014)

Bottom Line: An experiment with healthy animals was conducted and the MRI pictures we obtained show a better contrast with the AguIX compared to the DOTAREM® for the same amount of injected gadolinium in the animal.In comparison, the median survival time is increased to 102.5 days with AGuIX particles showing their interest in this nanomedicine protocol.This remarkable radiosensitizing effect could be explained by the persistent tumor uptake of the particles, inducing a significant nanoscale dose deposition under irradiation.

View Article: PubMed Central - PubMed

Affiliation: ID17 Biomedical Beamline, European Synchrotron Radiation Facility, 6 rue Jules Horowitz, 38000 Grenoble, France.

ABSTRACT

AGuIX nanoparticles are formed of a polysiloxane network surrounded by gadolinium chelates. They present several characteristics. They are easy to produce, they present very small hydrodynamic diameters (<5 nm) and they are biodegradable through hydrolysis of siloxane bonds. Such degradation was evaluated in diluted conditions at physiological pH by dynamic light scattering and relaxometry. AGuIX nanoparticles are also known as positive contrast agents and efficient radiosensitizers. The aim of this paper is to compare their efficiency for magnetic resonance imaging and radiosensitization to those of the commercial gadolinium based molecular agent: DOTAREM®. An experiment with healthy animals was conducted and the MRI pictures we obtained show a better contrast with the AguIX compared to the DOTAREM® for the same amount of injected gadolinium in the animal. The better contrast obtained after injection of Aguix than DOTAREM® is due to a higher longitudinal relaxivity and a residential time in the blood circulation that is two times higher. A fast and large increase in the contrast is also observed by MRI after an intravenous injection of the AGuIX in 9 L gliosarcoma bearing rats, and a plateau is reached seven minutes after the injection. We established a radiotherapy protocol consisting of an irradiation by microbeam radiation therapy 20 minutes after the injection of a specific quantity of gadolinium. After microbeam radiation therapy, no notable difference in median survival time was observed in the presence or absence of gadolinium chelates (38 and 44 days respectively). In comparison, the median survival time is increased to 102.5 days with AGuIX particles showing their interest in this nanomedicine protocol. This remarkable radiosensitizing effect could be explained by the persistent tumor uptake of the particles, inducing a significant nanoscale dose deposition under irradiation.

No MeSH data available.


Related in: MedlinePlus

T1-weigthed images of the brain of a 9LGS bearing rat 1 day after intravenous injection of AGuIX nanoparticles.
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Fig4: T1-weigthed images of the brain of a 9LGS bearing rat 1 day after intravenous injection of AGuIX nanoparticles.

Mentions: A small increase in the signal was observed in the healthy tissue of the rats, followed by a rapid decrease a few minutes after the injection. Conversely, a significant enhancement of the MRI signal was noticed in the tumor. It reached a plateau about 7 minutes after the intravenous injection of the nanoparticles (See Figure 3). After 1 day, a weak MRI signal can be still visualized in the tumor due to the presence of the nanoparticles (See Figure 4). The persistence of the signal is due to the very slow leakage of the nanoparticles from the tumor. The capacity of the nanoparticles to remain in the tumor even hours after their injection is a real asset to determine an adapted radiotherapy protocol. Contrary to the gadolinium chelates that present a rapid elimination from the tumor, the nanoparticles are rapidly cleared from healthy tissues while conserving a high and relatively constant concentration in the tumor.Figure 4


Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment.

Le Duc G, Roux S, Paruta-Tuarez A, Dufort S, Brauer E, Marais A, Truillet C, Sancey L, Perriat P, Lux F, Tillement O - Cancer Nanotechnol (2014)

T1-weigthed images of the brain of a 9LGS bearing rat 1 day after intravenous injection of AGuIX nanoparticles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631720&req=5

Fig4: T1-weigthed images of the brain of a 9LGS bearing rat 1 day after intravenous injection of AGuIX nanoparticles.
Mentions: A small increase in the signal was observed in the healthy tissue of the rats, followed by a rapid decrease a few minutes after the injection. Conversely, a significant enhancement of the MRI signal was noticed in the tumor. It reached a plateau about 7 minutes after the intravenous injection of the nanoparticles (See Figure 3). After 1 day, a weak MRI signal can be still visualized in the tumor due to the presence of the nanoparticles (See Figure 4). The persistence of the signal is due to the very slow leakage of the nanoparticles from the tumor. The capacity of the nanoparticles to remain in the tumor even hours after their injection is a real asset to determine an adapted radiotherapy protocol. Contrary to the gadolinium chelates that present a rapid elimination from the tumor, the nanoparticles are rapidly cleared from healthy tissues while conserving a high and relatively constant concentration in the tumor.Figure 4

Bottom Line: An experiment with healthy animals was conducted and the MRI pictures we obtained show a better contrast with the AguIX compared to the DOTAREM® for the same amount of injected gadolinium in the animal.In comparison, the median survival time is increased to 102.5 days with AGuIX particles showing their interest in this nanomedicine protocol.This remarkable radiosensitizing effect could be explained by the persistent tumor uptake of the particles, inducing a significant nanoscale dose deposition under irradiation.

View Article: PubMed Central - PubMed

Affiliation: ID17 Biomedical Beamline, European Synchrotron Radiation Facility, 6 rue Jules Horowitz, 38000 Grenoble, France.

ABSTRACT

AGuIX nanoparticles are formed of a polysiloxane network surrounded by gadolinium chelates. They present several characteristics. They are easy to produce, they present very small hydrodynamic diameters (<5 nm) and they are biodegradable through hydrolysis of siloxane bonds. Such degradation was evaluated in diluted conditions at physiological pH by dynamic light scattering and relaxometry. AGuIX nanoparticles are also known as positive contrast agents and efficient radiosensitizers. The aim of this paper is to compare their efficiency for magnetic resonance imaging and radiosensitization to those of the commercial gadolinium based molecular agent: DOTAREM®. An experiment with healthy animals was conducted and the MRI pictures we obtained show a better contrast with the AguIX compared to the DOTAREM® for the same amount of injected gadolinium in the animal. The better contrast obtained after injection of Aguix than DOTAREM® is due to a higher longitudinal relaxivity and a residential time in the blood circulation that is two times higher. A fast and large increase in the contrast is also observed by MRI after an intravenous injection of the AGuIX in 9 L gliosarcoma bearing rats, and a plateau is reached seven minutes after the injection. We established a radiotherapy protocol consisting of an irradiation by microbeam radiation therapy 20 minutes after the injection of a specific quantity of gadolinium. After microbeam radiation therapy, no notable difference in median survival time was observed in the presence or absence of gadolinium chelates (38 and 44 days respectively). In comparison, the median survival time is increased to 102.5 days with AGuIX particles showing their interest in this nanomedicine protocol. This remarkable radiosensitizing effect could be explained by the persistent tumor uptake of the particles, inducing a significant nanoscale dose deposition under irradiation.

No MeSH data available.


Related in: MedlinePlus