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Sonodynamic therapy (SDT) is a promising novel treatment modality that has demonstrated impressive antineoplastic activity in both in vitro and in vivo studies 1.
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In an effort to improve HIFU, researchers have attempted to combine ultrasound with appropriate antineoplastic agents to generate a form of sonochemotherapy. Nevertheless, the limited success it has achieved, and the very promising in vivo data acquired from preclinical mammalian models have demonstrated the potential of ultrasound in cancer therapy. HIFU has attained mixed results in the clinic and is currently only available in clinical trials 8-11. Although other modalities of thermal ablation currently exist (radiofrequency ablation and microwave ablation), HIFU offers a distinct advantage over these methods in that it is the only non-invasive hyperthermic modality 5.
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In a manner very similar to ESWL, HIFU uses multiple ultrasound beams and focuses them on a selected focal area to generate temperatures of 60 ☌ or higher through the use of acoustic energy, inducing coagulative necrosis in the targeted tissue 5. This approach known as extracorporeal shockwave lithotripsy (ESWL) is now widely applied in the clinic (more than one million patients are treated annually with ESWL in the United States alone 4), and offers a modality by which to non-invasively break up calculi with minimal collateral damage through the use of externally applied, focused, high intensity acoustic pulses 2-4.ĭue to the unique direct shearing forces, as well as cavitation bubbles generated by high intensity ultrasound, these methodologies have been examined in cancer therapy for the treatment of castration-resistant prostate carcinoma and pancreatic adenocarcinoma in an approach known as high intensity focused ultrasound (HIFU) 5-8. Ultrasound ≥1 MHz is capable of safely disrupting urinary calculi (kidney stones) and biliary calculi (stones in the gallbladder or in the liver) in patients to reduce symptoms 2,3. Commercially available ultrasound generators come in frequencies ranging from 18-60 kHz, and full-scale wattages from 100-1,200 W.Īlthough ultrasound has long been used in the clinical setting for diagnostic imaging, it has been applied as a therapeutic modality only recently. The utility of low frequency ultrasound has also been extended to the industrial setting for welding, cleaning various materials, and in materials processing. Low frequency ultrasound in the 20-60 kHz range has been utilized in the laboratory as a means of generating emulsions, preparing cellular samples for nucleic acid extraction, for tissue disruption, and for a variety of other tests. Ultrasound refers to any oscillating sound pressure wave with a frequency greater than the upper limit of human auditory capacities (~ 20 kHz) 1. In addition, the effects of cholesterol-depleting and cytoskeletal-directed agents on potentiating ultrasonic sensitivity in neoplastic cells are discussed in order to elaborate on mechanisms of action conducive to sonochemotherapeutic approaches. This offers a means by which to reliably sonicate neoplastic cells at a level of consistency required for preclinical therapeutic assessment.
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The methodology for generating and applying low frequency ultrasound in a preclinical in vitro setting is presented to demonstrate that reproducible cell destruction can be attained in order to examine and compare the effects of sonication on neoplastic and normal cells. In addition, this method can be used in combination with specialized agents known as sonosensitizers to increase the extent of preferential damage exerted by ultrasound against neoplastic cells, an approach referred to as sonodynamic therapy (SDT). Low frequency ultrasound in the 20 to 60 kHz range is a novel physical modality by which to induce selective cell lysis and death in neoplastic cells.