Abstract
AGuIX are gadolinium-based nanoparticles developed mainly for imaging due to their MR contrast properties. They also have a potential role in radiation therapy as a radiosensitizer. We used MRI to quantify the uptake of AGuIX in pancreatic cancer cells, and TEM for intracellular localization. We measured the radiosensitization of a pancreatic cancer cell line in a low-energy (220 kVp) beam, a standard 6 MV beam (STD) and a flattening filter free 6 MV beam (FFF). We demonstrated that the presence of nanoparticles significantly decreases cell survival when combined with an X-ray beam with a large proportion of low-energy photons (close to the k-edge of the nanoparticles). The concentration of nanoparticles in the cell achieves its highest level after 15 min and then reaches a plateau. The accumulated nanoparticles are mainly localized in the cytoplasm, inside vesicles. We found that the 6 MV FFF beams offer the best trade-off between penetration depth and proportion of low-energy photons. At 10 cm depth, we measured a DEF20 % of 1.30 ± 0.47 for the 6 MV FFF beam, compared to 1.23 ± 0.26 for the 6 MV STD beam. Additional measurements with un-incubated nanoparticles provide evidence that chemical processes might also be contributing to the dose enhancement effect.
Highlights
Nanoparticles made from high-Z materials are promising agents to increase radiosensitivity of cancer cells during the application of radiation therapy. Hainfeld et al (2004, 2008) demonstrated therapeutic enhancement with gold nanoparticles (GNP) in a 250 kVp X-ray beam
Further studies have confirmed the dose-enhancing effect of GNP in 6 MV X-ray beams, an energy range that is typically used for clinical radiation therapy (Detappe et al 2013; Berbeco et al 2011; Cho 2005; Jones et al 2010; Lin et al 2014; Robar et al 2002; McMahon et al 2008; Ngwa et al 2014)
The aim of the current study is to characterize the uptake of the AGuIX nanoparticles in pancreatic cancer cells by magnetic resonance imaging (MRI), and investigate the radiation dose enhancement effect attributable to AGuIX when irradiating the cells with a clinical linear accelerator at 6 MV
Summary
Nanoparticles made from high-Z materials are promising agents to increase radiosensitivity of cancer cells during the application of radiation therapy. Hainfeld et al (2004, 2008) demonstrated therapeutic enhancement with gold nanoparticles (GNP) in a 250 kVp X-ray beam. Further studies have confirmed the dose-enhancing effect of GNP in 6 MV X-ray beams, an energy range that is typically used for clinical radiation therapy (Detappe et al 2013; Berbeco et al 2011; Cho 2005; Jones et al 2010; Lin et al 2014; Robar et al 2002; McMahon et al 2008; Ngwa et al 2014). Even though gold nanoparticles may be efficient radiosensitizers, it remains difficult to measure their exact concentration within the tumor with current clinically available imaging methods. To address this issue, multimodal nanoparticles have been
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