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Updated: Apr 19, 2026
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Focused ultrasound-mediated drug delivery to pancreatic cancer in a mouse model
Natalya Rapoport1, Allison Payne2, Christopher Dillon1
1Department of Bioengineering, University of Utah, 36 S. Wasatch Dr., Room 3100, Salt Lake City, UT 84112, USA.
Background:
Many aspects of the mechanisms involved in ultrasound-mediated therapy remain obscure. In particular, the relative roles of drug and ultrasound, the effect of the time of ultrasound application, and the effect of tissue heating are not yet clear. The current study was undertaken with the goal to clarify these aspects of the ultrasound-mediated drug delivery mechanism.
Methods:
Focused ultrasound-mediated drug delivery was performed under magnetic resonance imaging guidance (MRgFUS) in a pancreatic ductal adenocarcinoma (PDA) model grown subcutaneously in nu/nu mice. Paclitaxel (PTX) was used as a chemotherapeutic agent because it manifests high potency in the treatment of gemcitabine-resistant PDA. Poly(ethylene oxide)-co-poly(d,l-lactide) block copolymer stabilized perfluoro-15-crown-5-ether nanoemulsions were used as drug carriers. MRgFUS was applied at sub-ablative pressure levels in both continuous wave and pulsed modes, and only a fraction of the tumor was treated.
Results:
Positive treatment effects and even complete tumor resolution were achieved by treating the tumor with MRgFUS after injection of nanodroplet encapsulated drug. The MRgFUS treatment enhanced the action of the drug presumably through enhanced tumor perfusion and blood vessel and cell membrane permeability that increased the drug supply to tumor cells. The effect of the pulsed MRgFUS treatment with PTX-loaded nanodroplets was clearly smaller than that of continuous wave MRgFUS treatment, supposedly due to significantly lower temperature increase as measured with MR thermometry and decreased extravasation. The time of the MRgFUS application after drug injection also proved to be an important factor with the best results observed when ultrasound was applied at least 6 h after the injection of drug-loaded nanodroplets. Some collateral damage was observed with particular ultrasound protocols supposedly associated with enhanced inflammation.
Conclusion:
This presented data suggest that there exists an optimal range of ultrasound application parameters and drug injection time. Decreased tumor growth, or complete resolution, was achieved with continuous wave ultrasound pressures below or equal to 3.1 MPa and drug injection times of at least 6 h prior to treatment. Increased acoustic pressure or ultrasound application before or shortly after drug injection gave increased tumor growth when compared to other protocols.
Insights
Optimizing focused ultrasound (FUS) parameters and drug timing is key for effective cancer therapy. Applying continuous wave FUS at specific pressures, at least 6 hours post-drug injection, significantly improved pancreatic cancer treatment in mice.
Area of Science:
- Oncology
- Biomedical Engineering
- Nanotechnology
Background:
- Mechanisms of ultrasound-mediated therapy, including drug and ultrasound roles, timing, and thermal effects, require clarification.
- Pancreatic ductal adenocarcinoma (PDA) is a challenging cancer, often resistant to standard chemotherapy.
Purpose of the Study:
- To elucidate the optimal parameters for ultrasound-mediated drug delivery in pancreatic cancer.
- To investigate the influence of ultrasound application timing and thermal effects on drug delivery efficacy.
Main Methods:
- Magnetic resonance imaging-guided focused ultrasound (MRgFUS) was employed in a subcutaneous PDA mouse model.
- Paclitaxel (PTX)-loaded nanoemulsions were administered, and MRgFUS was applied in continuous wave (CW) and pulsed modes at sub-ablative pressures.
- MR thermometry monitored temperature changes, and treatment timing relative to drug injection was varied.
Main Results:
- MRgFUS enhanced paclitaxel delivery, leading to positive treatment effects and complete tumor resolution in some cases.
- Continuous wave MRgFUS demonstrated superior efficacy compared to pulsed mode, likely due to higher temperatures and increased drug extravasation.
- Optimal results were achieved when MRgFUS was applied at least 6 hours after drug injection, with specific pressure thresholds (≤3.1 MPa) showing reduced tumor growth.
Conclusions:
- Optimal ultrasound parameters and drug injection timing are critical for maximizing therapeutic outcomes in ultrasound-mediated drug delivery.
- Continuous wave ultrasound below 3.1 MPa, applied 6 hours post-drug injection, significantly reduced tumor growth and achieved complete resolution in a PDA model.
- Deviations from optimal parameters, including higher acoustic pressure or earlier ultrasound application, resulted in increased tumor growth.
