Tumour reoxygenation after intratumoural hydrogen peroxide (KORTUC) injection: a novel approach to enhance radiosensitivity

Samantha Nimalasena; Selvakumar Anbalagan; Carol Box; Sheng Yu; Jessica K R Boult; Nigel Bush; Louise Howell; Victoria Sinnett; William Murphy; John Yarnold; Simon P Robinson; Navita Somaiah

doi:10.1038/s44276-024-00098-y

Tumour reoxygenation after intratumoural hydrogen peroxide (KORTUC) injection: a novel approach to enhance radiosensitivity

BJC Rep. 2024 Oct 8;2(1):78. doi: 10.1038/s44276-024-00098-y. eCollection 2024 Dec.

Authors

Affiliations

¹ Division of Radiotherapy & Imaging, The Institute of Cancer Research, London, UK.
² The Royal Marsden NHS Foundation Trust, London, UK.
³ Core Research Facilities, The Institute of Cancer Research, London, UK.
⁴ Biological Service Unit, The Institute of Cancer Research, London, UK.

^# Contributed equally.

Abstract

Background: KORTUC (0.5% hydrogen peroxide (H₂O₂) in 1% sodium-hyaluronate) releases cytotoxic levels of H₂O₂ in tissues after intratumoural injection. High levels of tumour control after radiotherapy plus KORTUC are reported in breast cancer patients. Here, we use human xenograft models to test the hypothesis that oxygen microbubbles released post-KORTUC are effective in modifying the hypoxic tumour microenvironment.

Methods and materials: Pimonidazole and Image-iT™ Red (live hypoxia marker) were utilised to assess dose-dependent changes in hypoxia post-H₂O₂ in HCT116 and LICR-LON-HN5 spheroids. Using a dual 2-nitroimidazole-marker technique and phospho-ATM we evaluated changes in hypoxia and reactive oxygen species (ROS) respectively, in HCT116 and LICR-LON-HN5 xenografts following intratumoural KORTUC.

Results: A significant reduction in Image-iT™ Red fluorescence was observed in spheroids 1 h post-H₂O₂ at ≥1.2 mM, maintained at 24 h. Ultrasound demonstrated sustained release of oxygen microbubbles within tumours, 1 h post-KORTUC. Hypoxia markers demonstrated significant tissue reoxygenation in both models post-KORTUC and significantly increased phospho-ATM foci reflecting increased ROS production.

Conclusion: Intratumoural KORTUC represents a novel oxygen delivery method, which can be exploited to enhance radiation response. If efficacy is confirmed in the ongoing phase 2 breast trial it could improve treatment of several tumour types where hypoxia is known to affect radiotherapy outcomes.