ESTRO meets Asia 2024 - Abstract Book

S252

Interdisciplinary – Radiobiology

ESTRO meets Asia 2024

after irradiation, providing evidence for the regulation of MDM2 by mettl3. Mathematical modeling of the p53 regulatory network showed that administering the appropriate dose of SAH resulted in an elevated level of p53 oscillatory activation, leading to an increase in the germination rate, surface area, and survival rate of irradiated organoids, as well as an improvement in the survival and body weight of mice. Furthermore, both organoid and mouse models showed an increase in the number of stem cells and a decrease in the amount of DNA damage.

Conclusion:

Overall, the present study shows that IR-responsive mettl3 is involved in IR-induced DNA damage repair in ISCs, probably by regulating the p53 oscillatory activation via MDM2 m6A modification, which may be a novel mechanism involved in the occurrence and development of RIII.

Keywords: p53 oscillatory activation, MDM2, m6A

288

Proffered Paper

Enhancing Radioresponse using Ultrasound-Stimulated Microbubbles in Murine Head and Neck Cancer

Hannah Bargh-Dawson 1 , Carol Box 1 , John Civale 1 , Graeme Birdsey 2 , Jeffrey Bamber 1 , Emma Harris 1

1 Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom. 2 National Heart & Lung Institute, Imperial College London, London, United Kingdom

Purpose/Objective:

Although advances have been made in radiotherapy treatment planning and delivery over recent decades, issues of normal tissue toxicities and radioresistance remain, particularly for patients with head and neck cancer (HNC). Emerging preclinical and clinical evidence has highlighted the potential of ultrasound-stimulated microbubbles (USMB) to enhance radiotherapy efficacy and allow dose de-escalation [1, 2, 3]. USMB modulate the tumour microenvironment (TME) in a highly localised manner by targeting the microvasculature, inducing biological effects such as vessel disruption, vasodilation, immune cell activation and infiltration, and enhanced vessel permeability [4]. This work aimed to assess the potential of USMB as radiosensitising agents in murine HNC models, and to understand the immunological and biological mechanisms underlying response to therapy.

Material/Methods:

C57BL/6 mice bearing subcutaneous murine oral carcinoma tumours (MOC1 and MOC2) were randomly allocated into i) no treatment ii) 8 Gy or iii) USMB and 8 Gy treatment groups once tumours reached 150 mm 3 . For USMB, intravenously administered Luminity® microbubbles were stimulated by a 1 MHz transducer for 5 minutes. A single dose of 8 Gy was delivered 6 hours after USMB using a Small Animal Radiation Research Platform. Dynamic contrast-enhanced ultrasound (DCE-US) imaging assessed changes in tumour vascularity and perfusion 48 hours, and 7 days post-treatment. Semi-quantitative metrics of tumour perfusion such as peak enhancement, wash-in time and wash-out time were derived from time-amplitude curves generated from DCE-US imaging data.