Ultrasound-Guided Microbubble-Assisted Delivery of Radiopharmaceutical Agents for Gastric Tumor Control.

Abstract

Background: Radiopharmaceutical therapy uses drugs with radioactive isotopes for targeted cancer treatment. However, its effectiveness in gastric cancer is often limited by poor tumor penetration, heterogeneous intratumoral distribution, and off-target radiation exposure. Ultrasound-guided microbubble-assisted delivery offers a noninvasive means to increase vascular permeability and enhance tumor-specific radiopharmaceutical uptake.

Methods: This study developed and evaluated an ultrasound-guided microbubble delivery system to enhance intratumoral radiopharmaceutical accumulation, therapeutic efficacy, and safety in gastric cancer. Ligand-functionalized, radiopharmaceutical-loaded microbubbles were administered intravenously in an orthotopic gastric tumor model. Tumors were localized by real-time ultrasound imaging and then exposed to focused ultrasound to induce controlled microbubble cavitation. Biodistribution was analyzed using positron emission tomography imaging. Tumor growth was monitored by serial ultrasound, and therapeutic response was assessed with histopathology and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. Radiation safety was determined by organ-specific biodosimetry.

Results: Microbubble activation significantly increased intratumoral uptake to 8.4-1.2%ID/g, compared with 3.0 - 0.6%ID/g for conventional delivery (p < 0.001). Tumor-to background ratios improved approximately 2.6-fold, and tumor volumes decreased by 58% relative to controls. Apoptotic indices reached 41.8 - 6.3% in treated tumors versus < 15% in controls; off-target organ uptake remained < 2.0% ID/g.

Conclusions: Ultrasound-guided, microbubble-assisted radiopharmaceutical administration increased tumor-specific absorption, slowed tumor development, and decreased systemic exposure, indicating a promising treatment strategy for gastric cancer.