ESTRO 2025 - Abstract Book

S3933

Radiobiology - Normal tissue radiobiology

ESTRO 2025

2601

Digital Poster Optimizing blood-brain barrier modulation with low-dose fractionated radiotherapy for effective CNS antibody delivery Pei-jing Li 1 , Ting Jin 1 , Yun Xing 2 , Yuan-yuan Chen 3 , Shuang Huang 1 , Feng Jiang 1 , Xiao-Zhong Chen 1 , Peng Guo 4 1 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China. 2 Medical School, Faculty of Medicine, Tianjin University, Hangzhou, China. 3 Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, China. 4 Clinical Translational Research Center, Hangzhou Institute of Medicine, Hanghzou, China Purpose/Objective: The blood-brain barrier (BBB) poses a major obstacle in the treatment of central nervous system (CNS) diseases, particularly for large-molecule therapeutics like monoclonal antibodies. Enhancing BBB permeability could revolutionize therapies for CNS disorders such as Alzheimer's disease and brain tumors. Here, we explored low dose fractionated radiotherapy (LDFR) as a novel strategy to transiently enhance BBB permeability and improve the penetration of monoclonal antibodies into normal murine brain tissue. Material/Methods: Wild mice and tumor mice models were used in this study. Antibody MRI probe and antibody fluorescence probe were used to display the distribution of antibodies in animals. Immunofluorescence staining and Light sheet imaging was designed to show the spatial distribution of antibodies in the brain. Single-cell RNA sequencing was conducted to explore the mechanism of radiation-induced enhancement of antibody trans-BBB penetration. Western blot, CoIP, and immune-histochemical staining were applied to verify the mechanism of this phenomenon. Results: Quantitative analysis reveals a 20.4-fold increase in trans-BBB antibody delivery post-LDFR compared to controls. Moreover, we quantitatively measured molecular weight dependence and temporal dynamics of BBB permeability upon LDFR. Mechanistically, single-cell RNA sequencing was employed to elucidate that FAT10 regulates the stability of S1P1 receptor through ubiquitin-like modification, disrupts endothelial glycocalyx renewal and repair, and mediates radiation-induced enhancement of biopharmaceutical trans-BBB penetration. Safety assessments indicated minimal off-target effects and no significant neurotoxicity, highlighting the potential of LDFR as a safe and effective method for enhancing CNS drug delivery.

Conclusion: Our findings offer critical insights into optimizing LDFR protocols for CNS-targeted therapies.

Keywords: Blood-brain barrier, drug delivery, radiotherapy

2735

Digital Poster Impaired DNA double-strand breaks repair in Friedreich’s Ataxia fibroblasts Rafka Challita 1 , Dana Tohme 1 , Charbel Feghaly 2 , Hanin Bou Hadir 2 , Walaa Chebli 2 , Elie Estephan 2 , Rana El-Hassan 1 , Sima Hussayni 1 , Wassim Abou Kheir 1 , Larry Bodgi 2,1 1 Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon. 2 Department of Radiation Oncology, American University of Beirut, Beirut, Lebanon