Ultrasound-Mediated Microbubble Disruption to Enhance Radiopharmaceutical Access to the Tumor Microenvironment in Immune-Resistant Lung Carcinoma.

Abstract

Background: Immune-resistant lung carcinoma poses a major hurdle for effective cancer treatment, largely due to its dense tumor microenvironment (TME) and the challenges of drug penetration. To boost the effectiveness of radiopharmaceuticals in this intricate TME, focused ultrasound-mediated microbubble cavitation (FUS-MMC) needs to enhance their accessibility. Current delivery methods often fall short, suffering from limited vascular permeability and insufficient tumor uptake. This results in less effective treatments and increased off-target toxicity. Methods: To address this issue, this article proposes a targeted delivery framework that utilizes FUS-MMC. This innovative technique involves administering microbubbles systemically and directing ultrasound precisely to disrupt the tumor's blood vessels and extracellular matrix temporarily. By using the FUS-MMC approach, the permeability of the TME is improved, allowing radiopharmaceuticals like 177Lu-DOTATATE to penetrate deeper into the tumor tissues. This enhanced access leads to a more even distribution and greater accumulation of therapeutic agents right at the tumor site. Results and Conclusion: FUS-MMC significantly boosts the efficiency of radiopharmaceutical delivery, reduces systemic exposure, and improves tumor response rates in models of immune-resistant lung carcinoma. This noninvasive and repeatable strategy represents a promising step forward in precision oncology and targeted cancer therapy.