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Application of Theranostic Gadolinium Based Nanoparticles Loaded in Next Generation Radiotherapy Biomaterials for Magnetic Resonance-Image-Guided Radiotherapy

R Mueller1,2,3*, M Moreau3,4,5, S Yasmin-Karim3,4, O Tillement6, R Berbeco3,4, J Hesser1,2,7,8, W Ngwa3,4,5, (1) Department Data Analysis and Modeling in Medicine, Mannheim Institute for Intelligent Systems in Medicine (MIISM), Heidelberg University, 69117 Heidelberg, Germany (2) Heidelberg University, 69117 Heidelberg, Germany (3) Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA (4) Harvard Medical School, Boston, MA 02115, USA (5) University of Massachusetts Lowell, Lowell, MA 01854, USA (6) Institut Lumière Matière, UMR5306, Université Lyon1-CNRS, Université de Lyon, Villeurbanne, France (7) Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, 69120 Heidelberg, Germany (8) Central Institute for Computer Engineering (ZITI), Heidelberg University, 68159 Mannheim, Germany


(Sunday, 7/12/2020) 11:30 AM - 12:30 PM [Eastern Time (GMT-4)]

Room: Track 2

Purpose: Theranostic nanoparticles (NPs) present new opportunities to enhance image-guided radiotherapy (IGRT). Radiotherapy (RT) biomaterials such as fiducial or beacons, which are routinely implanted in patients to ensure spatial accuracy, can be upgraded to smarter ones loaded with theranostic NPs. This study investigates the potential of next generation Smart Radiotherapy Biomaterials (SRBs) loaded with theranostic gadolinium-based nanoparticles (Gd NPs), which provide magnetic resonance imaging (MRI) contrast and can amplify damage to tumor cells during RT.

Methods: SRBs were fabricated using a mixture of Poly(lactic-co-glycolic) acid polymer and Dimethyl Sulfoxide with hollow core for high capacity Gd NP loading. Image-contrast using 7 T MRI was investigated in-vitro in agar gel and in-vivo in wild type C57/BL6 mice subcutaneously injected with Lewis Lung Carcinoma Cells LLC1. The release of NPs was quantified both in phantom and in-vivo.

Results: Relaxation rate was linearly fitted to Gd NP concentration with high confidence level (R² = 0.9843) and a detection threshold of 0.004 mmol/L. Gd NP loaded SRBs implanted in the tumor were clearly visible in MRI inside the tumor up to 14 days after implantation. Results showed degradation of SRBs polymer component (and hence release of NPs) via a signal decrease of 59.8 % in in-vivo experiments. In particular, 2.94 µg of Gd was released into the tumor volume during a 14 days period after SRB implantation.

Conclusion: Results show MRI is able to quantify Gd NP concentration highly accurate and sensitive. It enables for quantification of deposited dose in tissue. Hence, it represents the basis for a quantitative RT planning using NPs. In particular, MR-Linacs can monitor NP distribution over treatment time and hence would allow for a dynamic treatment planning scenario.

Funding Support, Disclosures, and Conflict of Interest: OT is the co-founder and CSO of NH Theraguix.


Calibration, MRI, Quantitative Imaging


IM/TH- MRI in Radiation Therapy: Development (new technology and techniques)

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