ESTRO 2021 Abstract Book

S193

ESTRO 2021

of a heated (25°C) water phantom with their right hind leg submerged in the water. The mice were irradiated with a single fraction (22 to 46Gy) in a 83-107MeV pencil scanning proton beam or, as reference, a clinical 6MV linac. For proton radiation, the leg was irradiated either in the center of a 3cm SOBP (LET = 1.2 KeV/um) or at the distal edge of the SOBP (LET=8.4 KeV/um). The endpoint was acute moist desquamation of the skin within 25 days post irradiation (Von der Maase H. Br J Radiol. 1984;57(680):697–707). Data collection continues for assessment of late side effects. Results A significant difference in ED50 (the dose producing acute skin damage in 50% of the mice) between distal edge SOBP and photons was found (33.2Gy (95% confidence interval 31.9-34.4Gy) (distal edge SOBP) and 37.5Gy (36.2- 38.9Gy) (photons). The difference between ED50 of central SOBP and photons was non- significant (ED50 central SOBP: 35.8Gy (34.8-36.8Gy). The corresponding RBE values were 1.05 (1.00-1.10) (central SOBP) and 1.13 (1.07-1.19) (distal edge SOBP). Conclusion The biological effect was enhanced at the distal edge of the SOBP despite a slightly lower physical dose, and the study thus demonstrates an increase in RBE toward the distal edge for early reacting normal tissue for high single doses. OC-0284 MAN1C1, a potential regulator of monocyte – endothelial cell interactions after irradiation S. Ladaigue 1 , A. Lefranc 1 , K. Baldé 1 , M. Quitoco 1 , E. Bacquer 1 , A. François 1 , V. Paget 1 , F. Milliat 1 , O. Guipaud 1 1 French institute of radiation protection and nuclear safety, Radiobiology of medical exposure laboratory, Fontenay-aux-roses, France Purpose or Objective Normal tissue damages associated with chronic infiltration of innate immune cells drive late normal tissue injury induced by radiotherapy. Macrophages may play a major role in these adverse effects, but little is known about the role and the recruitment of their precursors, the monocytes in irradiated tissues. Altered by ionizing radiation, vascular endothelial cells (ECs) participate in the recruitment of circulating cells, especially by overexpressing cell adhesion molecules but also by other as yet unknown mechanisms such as protein glycosylations. In a previous work, we have shown that irradiation of primary ECs downregulates the expression of the α-1,2-mannosidase IC (MAN1C1) gene, increases the level of endothelial high mannose-type N-glycans (HM) and enhances THP-1 adhesion in a HM-dependent manner. The present study aims to clarify the role of HM and MAN1C1 in two key steps of monocyte recruitment by irradiated ECs, i.e. endothelial adhesion and trans-endothelial migration (TEM). Materials and Methods In vitro, interactions of THP-1 monocytes with irradiated human primary ECs (HUVECs) at 20 Gy were evaluated by real-time imaging using video-microscopy and the IncuCyte live cell analysis system. The role of endothelial MAN1C1 on HM and on THP-1 interactions with ECs was evaluated by gene expression inhibition and overexpression with siRNA and lentiviral vectors. The impact of MAN1C1 modulation on HM was assessed by flow cytometry using a fluorescent lectin that binds HM (concanavalin A). In vivo , the role of HM on monocyte/macrophages recruitment in irradiated tissues was evaluated by immunohistochemistry 3 and 7 days after abdominal irradiation in mice, following by repeated injections of two different lectins that bind HM (concanavalin A and cyanovirin-N). Results We show here that siRNA against the MAN1C1 gene administered to HUVECs increased THP-1 adhesion under flow and as well as the level of HM on HUVECs. First results also suggest that overexpression of MAN1C1 reduced THP-1 adhesion on irradiated HUVECs under flow and decreased the level of HM. To study the involvement of MAN1C1 in TEM, we developed a robust tool thanks to the Incucyte. We show that irradiation of HUVECs stimulates TEM of THP-1 in a dose-dependent manner. Interestingly, TEM was impaired by administration of siRNA against man1c1 and was increased with MAN1C1 overexpression. Finally, the impact of lectins administration on the infiltration of monocytes/macrophages after abdominal irradiation is being evaluated and will be presented in this work. Conclusion Altogether, our results suggest that endothelial MAN1C1 regulates the recruitment of monocytes at different steps following irradiation through HM. The questions remain to know if these glycosylations are also a key component to recruit monocytes/macrophages in irradiated tissues and if these glycans may be targeted to modulate innate infiltration and limit radiation adverse effects induced by radiotherapy. OC-0285 Differential neurocognitive response after partial brain proton irradiation D. Voshart 1 , F. van Buuren-Broek 1 , M. Klaver 1 , A. Scholma 1 , P. van Luijk 1 , R. Coppes 1 , L. Barazzuol 1 1 UMCG, Radiation Oncology, Groningen, The Netherlands Purpose or Objective Proton therapy is increasingly being used as an alternative to conventional photon-based radiotherapy to reduce normal tissue radiation dose and side effects in the treatment of brain tumors. Due to their physical properties, protons allow the potential sparing of brain regions that contribute the most to the development of neurocognitive dysfunction. However, current knowledge on regional responses is largely limited to the hippocampus. This study aims to identify which brain regions are most vulnerable to radiation and might increase the risk of neurocognitive dysfunction. Materials and Methods High-precision brain irradiation with 14 Gy protons (150 MeV) was delivered to 100%, 50% anterior and 50% posterior sub-volumes of the rat brain. Cognitive function was measured at different time points using the Novel Object Recognition test, the Barnes maze test and the Rotarod test. Additionally, the effects of partial brain proton irradiation on the innate neuro-inflammatory response were analyzed by semi-automatically