Delivery of Liposomal Doxorubicin (Doxil) in a Breast Cancer Tumor Model: Investigation of Potential Enhancement by Pulsed-High Intensity Focused Ultrasound Exposure

Frenkel, Victor; Etherington, Amena; Greene, Maiya; Quijano, Jade; Xie, Jianwu; Hunter, Finie; Dromi, Sergio; Li, King C.

doi:10.1016/j.acra.2005.08.024

Cited by 132 publications

(134 citation statements)

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“…pFUS exposures similar to those employed in the present study have been used to non-invasively and nondestructively enhance the delivery of a variety of systemically administered agents in murine solid tumors including plasmid DNA (Dittmar et al, 2005), small molecules (Poff et al, 2008), nanoparticles (Frenkel et al, 2006), and monoclonal antibodies (Khaibullina et al, 2008). More recently, in a study in the murine skeletal muscle, the same exposures were shown to enhance the delivery of both systemically and locally administered nanoparticles (Hancock et al, 2009).…”

Section: Discussionmentioning

confidence: 96%

“…Although changes in peak displacements were not observed, significant increases in the time required for the tissue to return back to its initial, pre-treatment state was found in all the treated tumors. Previous studies in a variety of tumors models, including HNSCC, have shown that pFUS exposures do not cause damage to the tissue (Dittmar et al, 2005;Frenkel et al, 2006;Khaibullina et al, 2008). The increase in the relaxation time in the treated tumors, which essentially indicates a reduction in tissue elasticity, must have then occurred from a decrease in the amount of fluid in the tumors.…”

Section: Figmentioning

confidence: 99%

“…Pulsed FUS (pFUS) exposures were carried out as previously described in Frenkel et al (2006). Mice were anesthetized with inhalation isofluorane (2%) during the entire exposure process.…”

Section: Pfus Exposuresmentioning

confidence: 99%

“…As a result, temperature elevations may be just a few degrees Celsius (and hence non-destructive), allowing for more delicate, non-thermal mechanisms to occur (Frenkel, 2008). pFUS exposures have demonstrated the ability to noninvasively enhance the delivery of a variety of systemically administered agents to solid tumors, including small molecules (Poff et al, 2008), plasmid DNA (Dittmar et al, 2005), monoclonal antibodies (Khaibullina et al, 2008), and nanoparticles (Dittmar et al, 2005;Frenkel et al, 2006). More recently, these exposures were shown to enhance the distribution of locally administered nanoparticles in skeletal muscle (Hancock et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Pulsed focused ultrasound exposures enhance locally administered gene therapy in a murine solid tumor model

Ziadloo

Xie

Frenkel

2013

The Journal of the Acoustical Society of America

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Gene therapy by intratumoral injection is a promising approach for treating solid tumors. However, this approach has limited success due to insufficient distribution of gene vectors used for gene delivery. Previous studies have shown that pulsed-focused ultrasound (pFUS) can enhance both systemic and local delivery of therapeutic agents in solid tumors and other disease models. Here, murine squamous cell carcinoma flank tumors were treated with single intratumoral injection of naked tumor necrosis factor-alpha (TNF-a) plasmid, either with or without a preceding pFUS exposure. The exposures were given at 1 MHz, at a spatial average, temporal peak intensity of 2660 W cm -2 , using 50 ms pulses, given at a pulse repetition frequency of 1 Hz. One hundred pulses were given at individual raster points, spaced evenly over the projected surface of the tumor at a distance of 2 mm. Exposures alone had no effect on tumor growth. Significant growth inhibition was observed with injection of TNF-a plasmid, and tumor growth was further inhibited with pFUS. Improved results with pFUS correlated with larger necrotic regions in histological sections and improved distribution and penetration of fluorescent surrogate nanoparticles. Electron microscopy demonstrated enlarged gaps between cells in exposed tissue, and remote acoustic palpation showed decreases in tissue stiffness after pFUS. Combined, these results suggest pFUS effects may be reducing barriers for tissue transport and additionally lowering interstitial fluid pressure to further improve delivery and distribution of injected plasmid for greater therapeutic effects. This suggests that pFUS could potentially be beneficial for improving local gene therapy treatment of human malignancies.

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Section: Discussionmentioning

confidence: 96%

Section: Figmentioning

confidence: 99%

“…Pulsed FUS (pFUS) exposures were carried out as previously described in Frenkel et al (2006). Mice were anesthetized with inhalation isofluorane (2%) during the entire exposure process.…”

Section: Pfus Exposuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pulsed focused ultrasound exposures enhance locally administered gene therapy in a murine solid tumor model

Ziadloo

Xie

Frenkel

2013

The Journal of the Acoustical Society of America

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“…A number of other applications of FUS, such as cardiac ablation (84), gene and drug delivery (85)(86)(87)(88), and stroke therapy (89) have also been investigated and are poised to have a large impact. These techniques have largely been investigated without image guidance.…”

Section: Future Development Of Technologymentioning

confidence: 99%

Current status and future potential of MRI‐guided focused ultrasound surgery

Jólesz

McDannold

2008

Magnetic Resonance Imaging

112

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The combination of the imaging abilities of magnetic resonance imaging (MRI) with the ability to delivery energy to targets deep in the body noninvasively with focused ultrasound presents a disruptive technology with the potential to significantly affect healthcare. MRI offers precise targeting, visualization, and quantification of temperature changes and the ability to immediately evaluate the treatment. By exploiting different mechanisms, focused ultrasound offers a range of therapies, ranging from thermal ablation to targeted drug delivery. This article reviews recent preclinical and tests clinical of this technology. WHILE ITS POTENTIAL has been recognized for decades (1-4), focused ultrasound (FUS) therapy has been in the incubation phase for a long time. Although it has been tested in numerous animal experiments, its widespread clinical realization has lagged, primarily due to the lack of intraprocedural accurate temperature monitoring. When the idea of MRI-guidance was introduced in connection with FUS and MRI thermometry during sonication was demonstrated (5,6), it was anticipated that MR-guided FUS surgery (MRgFUS) would be widely accepted clinically within a few years. Despite these early expectations, there has been relatively slow progress in the clinical implementation of MRgFUS.Early development concentrated primarily on breast tumors (benign fibroadenoma (7,8) and malignant breast cancer (9,10)). These early implementations of the MRgFUS technology motivated the improvement of transducer technology from single-element transducers to MRI-compatible multielement phase arrays (11). There was also significant progress in MRI thermometry and its use to monitor and control sonications. Importantly, too, methods were developed to robustly quantify temperature changes (12). At first, only 2D temperature maps were obtained by MRI to allow for accurate targeting of the beam (13). Later these thermal images were used to generate maps of the thermal dose (14) that could then be used to tailor the energy deposition using closed-loop feedback control (15). This preclinical work led to the development of the first commercial system by InSightec (Haifa, Israel), the Exablate 2000, the first implementation of a fully integrated MRgFUS system that combined a phased array transducer, a computer-controlled robotic positioner, and a workstation that integrated control based on MR thermometry.The early limited clinical trials of breast tumor treatment (8 -10,16,17) were followed by the first major clinical application: the noninvasive therapy of benign uterine fibroids (18,19). The successful Phase I trial was followed by a multicenter . These clinical trials led to the approval of this technology for the treatment of uterine fibroids in several countries, including the United States. Examples of MR thermometry and postablation imaging of a uterine fibroid ablation are shown in Figure 1.The success of uterine fibroid ablation has invigorated the entire field. Technology has rapidly improved and clinical applications ke...

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Liposomes and Drug Delivery

Antimisiaris

Kallinteri

Fatouros³

2010

Pharmaceutical Sciences Encyclopedia

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Liposomes are vesicles in which an aqueous volume is entirely surrounded by a phospholipid membrane and their size can range between 30 and 50 nm up to several micrometers. Liposomes serve as a drug delivery system because of their versatile structure and because they are nontoxic, nonimmunogenic, and fully biodegradable. This chapter focuses on basic characteristics and applications of liposomes, their fate after in vivo administration by different routes, and other possible routes for in vivo administration of liposomes.

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Delivery of Liposomal Doxorubicin (Doxil) in a Breast Cancer Tumor Model: Investigation of Potential Enhancement by Pulsed-High Intensity Focused Ultrasound Exposure

Cited by 132 publications

References 26 publications

Pulsed focused ultrasound exposures enhance locally administered gene therapy in a murine solid tumor model

Pulsed focused ultrasound exposures enhance locally administered gene therapy in a murine solid tumor model

Current status and future potential of MRI‐guided focused ultrasound surgery

Liposomes and Drug Delivery

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