MO-FG-BRA-07: Theranostic Gadolinium-Based AGuIX Nanoparticles for MRI-Guided Radiation Therapy

Authors

  • Detappe A,

    1. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical, Boston, MA
    2. Institut Lumiere-Matiere, Villeurbanne, France
    3. Nano-H, St-Quentin Fallavier, France
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  • Rottmann J,

    1. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical, Boston, MA
    2. Institut Lumiere-Matiere, Villeurbanne, France
    3. Nano-H, St-Quentin Fallavier, France
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  • Kunjachan S,

    1. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical, Boston, MA
    2. Institut Lumiere-Matiere, Villeurbanne, France
    3. Nano-H, St-Quentin Fallavier, France
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  • Tillement O,

    1. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical, Boston, MA
    2. Institut Lumiere-Matiere, Villeurbanne, France
    3. Nano-H, St-Quentin Fallavier, France
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  • Berbeco R

    1. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical, Boston, MA
    2. Institut Lumiere-Matiere, Villeurbanne, France
    3. Nano-H, St-Quentin Fallavier, France
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Abstract

Purpose:

AGuIX are gadolinium-based nanoparticles, initially developed for MRI, that have a potential role in radiation therapy as a radiosensitizer. Our goal is to demonstrate that these nanoparticles can both be used as an MRI contrast agent, as well as to obtain local dose enhancement in a pancreatic tumor when delivered in combination with an external beam irradiation.

Methods:

We performed in vitro cell uptake and radiosensitization studies of a pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical 6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After injection of 40mM of nanoparticles, a biodistribution study was performed in vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation therapy studies were performed at the time point of maximum tumor uptake.

Results:

The concentration of AGuIX nanoparticles in Panc-1 pancreatic cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes with 0.3% of the initial concentration (5mg/g). Clonogenic assays show a significant effect (p<0.05) when the AGuIX are coupled with MV photon irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by both MRI and ICPMS 30 minutes after intravenous injection. For long term survival studies, the choice of the radiation dose is determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and 20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of the nanoparticles. A Logrank test is performed as a statistical test to evaluate the effect of the nanoparticles.

Conclusion:

The combination of the MRI contrast and radiosensitization properties of gadolinium nanoparticles reveals a strong potential for usage with MRI-guided radiation therapy.

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