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Updated: Jul 25, 2025
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in
Khan Mohammad Imran1,2, Benjamin Tintera2, Holly A Morrison2
1Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA 24061, USA.
Abstract:
Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.
Insights
Ultrasound cavitation with SonoTran Particles significantly enhances drug delivery into pancreatic tumors. This novel approach improves the penetration of cancer therapeutics like Cetuximab, gemcitabine, and paclitaxel in a large animal model.
Area of Science:
- Oncology
- Biomedical Engineering
- Pharmacology
Background:
- Pancreatic tumors present significant barriers to drug delivery, including high interstitial fluid pressure and dense stroma.
- Existing therapeutic strategies often struggle to achieve effective drug concentrations within these tumors.
- Ultrasound-induced cavitation is an emerging technology with potential to overcome these limitations.
Purpose of the Study:
- To evaluate the efficacy of ultrasound-mediated cavitation using SonoTran Particles for enhancing drug delivery in a large animal model of human pancreatic ductal adenocarcinoma (PDAC).
- To assess the in situ effectiveness of this approach under conditions mimicking clinical scenarios.
Main Methods:
- Human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors were surgically engrafted into immunocompromised pigs.
- Animals received intravenous injections of Cetuximab, gemcitabine, and paclitaxel, followed by SonoTran Particles.
- Focused ultrasound was applied to target specific tumors, inducing cavitation, while other tumors served as controls within the same animals.
Main Results:
- Ultrasound-mediated cavitation significantly increased intra-tumor concentrations of Cetuximab (477%), gemcitabine (148%), and paclitaxel (193%).
- The large animal model successfully recapitulated key features of human PDAC tumors.
- SonoTran Particles combined with ultrasound demonstrated improved therapeutic delivery in pancreatic tumors.
Conclusions:
- Ultrasound-induced cavitation, when combined with gas-entrapping particles like SonoTran Particles, effectively enhances the delivery of multiple cancer therapeutics into pancreatic tumors.
- This approach shows promise for improving treatment efficacy in patients with pancreatic cancer.
- The study validates the potential of this technology in a clinically relevant large animal model.
