Radiosensitization of Allogenic Subcutaneous C6 Glioma Model with Focused Ultrasound-Induced Mild Hyperthermia

Author:

Xu Zhiyuan1,Schlesinger David1,Drainville Robert Andrew2ORCID,Moore David3,Pramoonjago Patcharin4,Sheehan Jason1,Padilla Frederic35ORCID

Affiliation:

1. Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA 22903, USA

2. LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, F-69003 Lyon, France

3. Focused Ultrasound Foundation, Charlottesville, VA 22903, USA

4. Department of Pathology, University of Virginia Health System, Charlottesville, VA 22903, USA

5. Department of Radiology, University of Virginia Health System, Charlottesville, VA 22903, USA

Abstract

The radiosensitization potential of focused ultrasound (FUS)-induced mild hyperthermia was assessed in an allogenic subcutaneous C6 glioma tumor model in rats. Mild hyperthermia at 42 °C was induced in tumors using a single-element 350 kHz FUS transducer. Radiation was delivered with a small animal radiation research platform using a single-beam irradiation technique. The combined treatment involved 20 min of FUS hyperthermia immediately before radiation. Tumor growth changes were observed one week post-treatment. A radiation dose of 2 Gy alone showed limited tumor control (30% reduction). However, when combined with FUS hyperthermia, there was a significant reduction in tumor growth compared to other treatments (tumor volumes: control—1174 ± 554 mm3, FUS-HT—1483 ± 702 mm3, 2 Gy—609 ± 300 mm3, FUS-HT + 2 Gy—259 ± 186 mm3; ANOVA p < 0.00001). Immunohistological analysis suggested increased DNA damage as a short-term mechanism for tumor control in the combined treatment. In conclusion, FUS-induced mild hyperthermia can enhance the effectiveness of radiation in a glioma tumor model, potentially improving the outcome of standard radiation treatments for better tumor control.

Funder

Focused Ultrasound Foundation

Publisher

MDPI AG

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