AGuIX nanoparticles as a promising platform for image-guided radiation therapy

Alexandre Detappe, Sijumon Kunjachan, Joerg Rottmann, James Robar, Panagiotis Tsiamas, Houari Korideck, Olivier Tillement, Ross Berbeco

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.