Related Experiment Video
Updated: Dec 19, 2025
Sonodynamic Therapy for the Treatment of Glioblastoma Multiforme in a Mouse Model Using a Portable Benchtop Focused Ultrasound System
Published on: February 10, 2023
Fluorescein-mediated sonodynamic therapy in a rat glioma model
Francesco Prada1,2,3, Natasha Sheybani4, Andrea Franzini5,6
1Department of Neurological Surgery, University of Virginia Health Science Center, Charlottesville, VA, USA. francesco.prada@istituto-besta.it.
Introduction:
Malignant gliomas have a dismal prognosis and significant efforts are being made to develop more effective treatments. Sonodynamic therapy (SDT) is an emerging modality for cancer treatment which combines ultrasound with sonosensitizers to produce a localized cytotoxic effect. The aim of this study is to demonstrate the efficacy of SDT with fluorescein (FL) and low-intensity focused ultrasound in inhibiting the growth of ectopic gliomas implanted in the rat's subcutaneous tissue.
Methods:
In vivo cytotoxicity of FL-SDT was evaluated in C6 rat glioma cells which were inoculated subcutaneously. Tumor specific extracellular FL extravasation and accumulation was assessed with IVIS imaging in rats receiving systemic FL. Effects of FL-SDT with focused low-intensity ultrasound on tumor growth, and histological features of the rat's tumors were investigated. Treatment related apoptosis and necrosis were analyzed using hematoxylin & eosin, and apoptosis-specific staining.
Results:
IVIS imaging revealed a high degree of FL accumulation within the tumor, with a nearly threefold increase in tumoral epifluorescence signal over background. SDT significantly inhibited outgrowth of ectopic C6 gliomas across all three FUS exposure conditions. TUNEL and active caspase-3 staining did not reveal conclusive trends across control and SDT condition for apoptosis.
Conclusion:
Our results suggest that SDT with FL and low-intensity FUS is effective in inhibiting the growth of ectopic malignant gliomas in rats. The selective FL extravasation and accumulation in the tumor areas where the blood-brain barrier is damaged suggests the tumor-specificity of the treatment. The possibility to use this treatment in intracranial models and in human gliomas will have to be explored in further studies.
Insights
Sonodynamic therapy (SDT) using fluorescein (FL) and focused ultrasound (FUS) effectively inhibited ectopic glioma growth in rats. This approach shows promise for treating malignant gliomas by targeting tumor-specific accumulation of FL.
Area of Science:
- Oncology
- Biophysics
- Medical Imaging
Background:
- Malignant gliomas have poor prognoses, necessitating novel therapeutic strategies.
- Sonodynamic therapy (SDT) combines ultrasound and sonosensitizers for localized cancer treatment.
- Fluorescein (FL) is explored as a sonosensitizer for SDT.
Purpose of the Study:
- To evaluate the efficacy of SDT with fluorescein (FL) and low-intensity focused ultrasound (FUS) in inhibiting ectopic glioma growth in rats.
- To assess tumor-specific FL accumulation and its impact on tumor growth.
Main Methods:
- In vivo cytotoxicity of FL-SDT was assessed in C6 rat glioma cells implanted subcutaneously.
- Tumor-specific FL extravasation and accumulation were visualized using IVIS imaging.
- Tumor growth inhibition and histological changes were analyzed post-FL-SDT treatment.
Main Results:
- IVIS imaging confirmed significant FL accumulation within tumors.
- FL-SDT significantly inhibited ectopic C6 glioma outgrowth under all tested FUS conditions.
- Apoptosis markers (TUNEL, active caspase-3) did not show conclusive trends.
Conclusions:
- SDT with FL and low-intensity FUS demonstrates efficacy in inhibiting ectopic malignant glioma growth in rats.
- Selective FL accumulation suggests tumor-specificity, potentially related to blood-brain barrier disruption.
- Further research is warranted to explore SDT's potential in intracranial models and human gliomas.
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