Radiotherapeutic enhancement using ultrasound-stimulated microbubbles: a critical review

Area of Science:

• Oncology
• Biomedical Engineering
• Radiotherapy

Background:

• Ultrasound stimulated microbubbles (USMB) are investigated as radioenhancing agents due to their localized mechanical effects, potentially reducing normal tissue toxicity.
• Preclinical studies in human cancer models show improved tumor control with USMB combined with radiotherapy compared to radiation alone, leading to Phase I clinical trials.
• The primary proposed mechanism of action for USMB radioenhancement involves their role as vascular disrupting agents, though alternative theories exist.

Purpose of the Study:

• To review the current literature on the role of tumor vasculature in radiotherapy response.
• To examine the bioeffects of USMB on tumor vasculature.
• To explore the potential interplay between USMB-mediated vascular modulation and radiation-induced anti-tumor immunity.

Main Methods:

• Literature review focusing on tumor vasculature, USMB bioeffects, and USMB as radioenhancers.
• Exploration of USMB's impact on the tumor immune microenvironment.
• Analysis of existing clinical and preclinical data on USMB and radiotherapy.

Main Results:

• Most preclinical data support the radioenhancement effect of USMB.
• Clinical studies confirm the safety of USMB.
• USMB monotherapy can modify tumor immune microenvironments and induce vascular bioeffects, with outcomes dependent on acoustic parameters.
• Limited research exists on USMB's effect on immune cell infiltration post-treatment, with non-significant findings in one study.
• Variability in USMB treatment parameters across studies hinders direct comparisons.

Conclusions:

• Further investigation into USMB for radioenhancement is necessary.
• Elucidating the mechanism of action is crucial for clinical translation.
• Optimization of treatment parameters for USMB combined with radiotherapy is required.