Program Information
Theranostic Nanoparticles Improve Clinical MR-Guided Radiation Therapy
A Detappe1,2*, S Kunjachan1 , L Sancey2 , V Motto-Ros2 , O Tillement2 , R Berbeco1 , (1) Dana-Farber Cancer Institute, Boston, MA, (2) Institut Lumiere-Matiere, Lyon, FR,
Presentations
WE-FG-BRA-7 (Wednesday, August 3, 2016) 1:45 PM - 3:45 PM Room: Ballroom A
Purpose: MR-guided radiation therapy is a current and emerging clinical reality. We have designed and tested a silica-based gadolinium chelates nanoparticle (AGuIX) for integration with MR-guided radiation therapy. The AGuIX nanoparticles used in this study are a dual-modality probe with radiosensitization properties and better MRI contrast than current FDA-approved gadolinium chelates. In advance of an approved Phase I clinical trial, we report on the efficacy and safety in multiple animal models and clinically relevant radiation conditions. By modeling our study on current clinic workflows, we show compatibility with modern patient care, thus heightening the translational significance of this research.
Material/Methods: The dual imaging and therapy functionality of AGuIX was investigated in mice with clinical radiation beams while safety was evaluated in mice, and non-human primates after systemic injection of 0.25 mg/g of nanoparticles. MRI/ICP-MS were used to measure tumor uptake and biodistribution. Due to their small size (2-3 nm), AGuIX have good renal clearance (t1/2=19min). We performed in vitro cell uptake quantification and radiosensitization studies (clonogenic assays and DNA damage quantification). In vivo radiation therapy studies were performed with both 6MV and 6MV-FFF clinical radiation beams. Histology was performed to measure the increase in DNA damage in the tumor and to evaluate the toxicity in healthy tissues.
Results: In vitro and in vivo results demonstrate statistically significant increase (P < 0.01) in DNA damage, tumor growth supression and survival (+100 days) compared to radiation alone. Negligible toxicity was observed in all of the animal models. The combination of 6MV-FFF/AGuIX demonstrated a substantial dose enhancement compared to 6MV/AGuIX (DEF = 1.36 vs. 1.22) due to the higher proportion of low energy photons.
Conclusion: With demonstrated efficacy and negligible toxicity in mice and non-human primates, AGuIX is a biocompatible nanoplatform with strong translational potential for MR-guided radiation therapy.
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