ESTRO 2020 Abstract Book

S1009 ESTRO 2020

were found to range between 2.0 and 3.1 at 10% survival. Cellular morphology, adhesion ability and surface marker expression remained largely unaffected in MSCs even after high doses irrespective of the type of radiation. However, while the MSCs’ migratory capacity was preserved after photon and C12 irradiation, UV-B treatment significantly reduced cellular velocity of MSCs. The stem cells’ differentiation ability along the adipogenic, osteogenic and chondrogenic lineages was preserved after all forms of ionizing radiation, and expression of defining stem cell surface markers of MSCs was unaffected. Photon, C12 and UV irradiation resulted in a G2 phase cell cycle arrest and low apoptosis levels of MSCs. γH2AX foci as a marker for DNA double-strand breaks were efficiently repaired after photon and C12 irradiation. Similarly, repair of UV-B- induced CPDs was found to be more efficient in MSCs than in dermal fibroblasts. Conclusion This comparative analysis demonstrated that MSCs are relatively resistant to different types of ionizing radiation. The differentiation capacity as important prerequisite for the stem cells’ regenerative abilities remains largely intact after exposure to photon, C12 and UV-B irradiation. An efficient repair of radiation-induced DNA damage may contribute to the observed resistance. PO-1809 Parallel quantification of MR signal and radioenhancement of Gd nanoparticles for MR-based dosimetry P. Maury 1 , M. Shahin 1,2 , A. Darricau 2,3 , S. Ammari 4 , F. Lux 5 , O. Tillement 5 , A. Rouyar-Nicolas 2 , C. Chargari 2,6 , E. Deutsch 2,6 , S. Lacombe 1 , C. Robert 2,3 , E. Porcel 1 1 Institut des Sciences Moléculaires d'Orsay ISMO, Paris Sud/Paris Saclay University, Orsay, France ; 2 Institut Gustave Roussy IGR, U1030 Molecular Radiotherapy, Villejuif, France ; 3 Institut Gustave Roussy IGR, Department of Medical Physics, Villejuif, France ; 4 Institut Gustave Roussy IGR, Department of Diagnostic Radiology, Villejuif, France ; 5 Institut Lumière Matière ILM, Claude Bernard University, Villeurbanne, France ; 6 Institut Gustave Roussy IGR, Department of Radiotherapy, Villejuif, France Purpose or Objective Several formulations of heavy metal based radiosensitizing nanoparticles (NPs) are in development. While increasing locally the energy deposit, these nanoparticles are posing the challenge of dose quantification. Gadolinium based NPs (AGuIX®) are currently developed as theranostic tools. These nanoagents accumulate in the tumor and act as radio-enhancers and MRI contrast agents. The objective of the ongoing project is to conduct a parallel NP concentration response assessment of MRI T1 relaxation and irradiated tumor cell killing. These measures are prerequisites for precise MRI based assessment of radiation cell kill increase by NP. Material and Methods First, a calibration curve giving the relaxation time modification (T1 mapping) of the MR signal as a function of the concentration of AGuIX® was established using an Eurospin T05 phantom. The AGuIX® concentration inside the tumor, based on MR images of three patients enrolled in a clinical trial combining the NPs to chemoradiation- brachytherapy in cervix cancer, was then determined. Moreover, 3D tumor models were prepared. There were composed of HeLa cells embedded in collagen. These models were incubated with AGuIX® following different conditions of time and concentration. Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) was performed on the Poster: Radiobiology track: Radiobiology of particles and heavy ions

3D models to quantify the AGuiX® content and determine which combination allowed to reproduce at best NP concentration evaluated in the patients. The models were finally irradiated with a 6MV rotational beam or a High Dose Rate (HDR) 192 Ir source, with increasing doses from 1 to 6 Gy. Survival curves were established to quantify the increase of the biological effect of this new therapeutic combination. Results A monotonous relation between AGuIX® concentration and T1 relaxation times was obtained (Figure 1). Mean tumor concentrations varying between 47 and 81µmol/L were determined for the three patients. Incubation of the 3D models with AGuIX® concentration of 0.5mmol/L during 4h allows to reproduce at best NP tumor concentrations encountered in the clinical trial. Results of the first irradiations showed a neat amplification effect in presence of nanoparticles when the 3D models were irradiated with a 6MV source (Figure 2). At 2Gy, the enhancement ratio was about 69%.

Conclusion These data will contribute to the integration of MRI based NPs quantification into specific radiotherapy dosimetric plans and confirm the theragnostic properties of AGuIX at clinically relevant concentrations.

Poster: Radiobiology track: Tumour microenvironment

PO-1810 Determining the boundaries of the FLASH effect B. Rothwell 1 , N. Kirkby 1,2 , M. Merchant 1,2 , A. Chadwick 1,2 , M. Lowe 1,3 , R. Mackay 1,3 , K. Kirkby 1,2 1 University of Manchester, Division of Cancer Sciences, Manchester, United Kingdom ; 2 The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom ; 3 The Christie NHS Foundation Trust, Christie Medical Physics and Engineering, Manchester, United Kingdom Purpose or Objective Ultra-high dose rate, or ‘FLASH’, radiotherapy is an area of worldwide interest, after studies have demonstrated normal-tissue-sparing advantages over conventional irradiation, while apparently retaining tumour control 1 . Currently, there is a distinct lack of understanding of the underlying mechanisms behind this effect. Many early reports have discussed radiation-induced oxygen depletion as a possible explanation for normal-tissue sparing, but this still needs further investigation. There is a wealth of knowledge of the radiobiological effects of hypoxia which can be used to explore this hypothesis further. This work is aimed at determining whether oxygen depletion can feasibly explain the normal-tissue-sparing effect of FLASH. Material and Methods Cellular automata techniques have been employed to solve a model of oxygen diffusion and consumption in cells, and to investigate how these are affected by ultra-high-dose- rate irradiation.