Hyperthermia-enhanced targeted drug delivery using magnetic resonance-guided focussed ultrasound: a pre-clinical study in a genetic model of pancreatic cancer

Farr, Navid; Wang, Yak-Nam; DʼAndrea, Samantha; Starr, Frank; Partanen, Ari; Gravelle, Kayla; McCune, Jeannine S.; Risler, Linda J.; Whang, Stella; Chang, Amy; Hingorani, Sunil R.; Lee, Donghoon; Hwang, Joo Ha

doi:10.1080/02656736.2017.1336675

Cited by 37 publications

(34 citation statements)

References 50 publications

(48 reference statements)

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“…HIFU guided by noninvasive MR thermometry is presently pursued primarily to induce local mild hyperthermia as a trigger for localized tumor-specific drug release from drugs encapsulated in thermosensitive liposomes [268]. Phantom tests with the ExAblate 2100 HIFU ablation system (InSightec Ltd, Haifa, Israel) [269,270] and preclinical tests with the Sonalleve system (Profound Medical Inc., Mississauga, Canada) have demonstrated the feasibility of inducing a stable MR controlled temperature rise [271][272][273] resulting in significantly enhanced ThermoDox delivery in mouse [274], rat [275], rabbit [276] and pig models [277]. Using the electronic beam steering of a single HIFU focus limits the size of the maximum volume with a stable elevated temperature level to a few cubic centimeters.…”

Section: Scanned Focused Ultrasoundmentioning

confidence: 99%

“…Thermal ablation is now more popular than application of hyperthermia as radiosensitizer or chemosensitizer, and the rapid rise of HIPEC and hyperthermic chemotherapy for NMIBC testify that combination of hyperthermia with chemotherapy is growing faster than combination of hyperthermia with radiotherapy, which is also associated with a different focus in device development. A breakthrough in heat-triggered tumor targeted drug delivery is one trend that would further strengthen popularity of the combination with chemotherapy [70,268,[274][275][276][277]. Finally, the recent trend to combine thermal therapies with immunotherapies has demonstrated significant potential to address recurrence and metastasis in preclinical and clinical pilot studies [425][426][427][428].…”

Section: Future Perspectivesmentioning

confidence: 99%

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Heating technology for malignant tumors: a review

Kok

Cressman

Ceelen

et al. 2020

International Journal of Hyperthermia

275

188

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The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors.

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Section: Scanned Focused Ultrasoundmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Heating technology for malignant tumors: a review

Kok

Cressman

Ceelen

et al. 2020

International Journal of Hyperthermia

275

188

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“…Steering capabilities of an acoustic lens for transcranial therapy: numerical and experimental studies Guillaume Maimbourg 1,2,3,4 , Alexandre Houdouin 1,2,3 , Thomas Deffieux 1,2,3 , Mickael Tanter 1,2,3 and Jean-François Aubry A single-element transducer with a 61mm radius of curvature and a 67mm aperture (H101 MR, Sonic Concepts, Bothell, USA) was used to achieve transcranial focusing. It was operated at its resonance frequency (914kHz), which was determined from the analysis of its complex impedance against frequency, using a vector network analyzer (ZVL, Rohde & Schwarz, Munich, Germany).…”

Section: A Transducermentioning

confidence: 99%

“…Focused ultrasound therapies have seen clinical applications for a growing number of pathologies: prostate [1,2] or pancreatic [3,4] cancers, bone metastases [5,6], uterine fibroids [7][8][9], or essential tremor [10][11][12]. It complements or even advantageously replaces surgery-based conventional methods.…”

Section: Introductionmentioning

confidence: 99%

Steering Capabilities of an Acoustic Lens for Transcranial Therapy: Numerical and Experimental Studies

Maimbourg

Houdouin

Thomas

et al. 2020

IEEE Trans. Biomed. Eng.

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Brain therapy by transcranial focused ultrasound needs to compensate for the delays locally induced by the skull. The patient-specific phase profile is currently generated by a multi-element array with a growing number of elements. We recently introduced a disruptive approach, consisting in using a single element transducer coupled to an acoustic lens of controlled thickness: by adjusting the local thickness of the lens, we were able to induce a phase difference which compensated that of the skull. Nevertheless, such an approach suffers from an apparent limitation: the lens is a priori designed for one specific target. In this paper, we demonstrate the possibility of taking advantage of the isoplanatic angle of the aberrating skull in order to steer the focus by mechanically moving the transducer/acoustic lens pair around its initial focusing position. This study, conducted on three human skull samples, confirms that tilting of the transducer with the lens restores a single focus at 914 kHz for a steering up to 11mm in the transverse direction, and 10mm in the longitudinal direction, around the initial focal region. Acoustic lens, transcranial ultrasound, therapeutic ultrasound

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“…Both preclinical and clinical results have demonstrated clinical efficiency of direct ablation and treatment by HIFU in areas such as prostate cancer, uterine fibroids, breast cancer, thyroid cancer, bone metastasis, essential tremor, brain tumors, pancreas cancer, and liver cancer . In these applications, HIFU systems are often combined with magnetic resonance imaging systems (MR) as integrated therapeutic systems, with MR guiding the positioning of the HIFU focal point in the organ being target for treatment, so‐called magnetic resonance‐guided focused ultrasound (MRgFUS).…”

Section: Introductionmentioning

confidence: 99%

High‐frequency (20‐MHz) high‐intensity focused ultrasound (HIFU) system for dermal intervention: Preclinical evaluation in skin equivalents

Bove¹,

Zawada²,

Serup

et al. 2019

Skin Research and Technology

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Background High‐intensity focused ultrasound (HIFU) for non‐invasive treatment of a range of internal pathologies including cancers of major organs and cerebral pathologies is in exponential growth. Systems, however, operate at relatively low frequencies, in the range of 200‐2000 kHz as required for deep axial penetration of the body. HIFU utilizing frequencies in excess of 15 MHz has so far not been explored, but presents an opportunity to extend the HIFU modality to target specific dermal lesions and small animal research. Materials and methods A new 20‐MHz HIFU system (TOOsonix ONE‐R) with narrow focus corresponding to the dermis was studied in acoustic skin equivalents, for example, in a tissue‐mimicking gel and in bovine liver. HIFU lesion geometry, depth, and diameter were determined. The temperature increase in the focal point was measured as a function of acoustic power and the duration of HIFU exposure. Results The system produces highly reproducible ultrasound lesions with predictable and configurable depths of 1‐2 mm, thus corresponding to the depth of the human dermis. The lesion geometry was elongated triangular and sized 0.1‐0.5 mm, convergent to a focal point skin deep. Focal point temperature ranged between 40 and 90°C depending on the chosen setting. Observations were confirmed ex vivo in bovine liver and porcine muscle. Variation of acoustic power and duration of exposure produced linear effects in the range of the settings studied. Thus, effects could be adjusted within the temperature interval and spatial field relevant for clinical therapy and experimental intervention targeting the dermal layer of human skin. Conclusion The tested 20‐MHz HIFU system for dermal applications fulfilled key prerequisite of narrow‐field HIFU dedicated to cutaneous applications regarding reproducibility, geometry, and small size of the applied ultrasound lesions. Controlled adjustment of acoustic lesions within the temperature range 40‐90°C qualifies the system for a range of non‐ablative and ablative applications in dermatological therapy.

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Hyperthermia-enhanced targeted drug delivery using magnetic resonance-guided focussed ultrasound: a pre-clinical study in a genetic model of pancreatic cancer

Cited by 37 publications

References 50 publications

Heating technology for malignant tumors: a review

Heating technology for malignant tumors: a review

Steering Capabilities of an Acoustic Lens for Transcranial Therapy: Numerical and Experimental Studies

High‐frequency (20‐MHz) high‐intensity focused ultrasound (HIFU) system for dermal intervention: Preclinical evaluation in skin equivalents

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