Micron-sized PFOB liquid core droplets stabilized with tailored-made perfluorinated surfactants as a new class of endovascular sono-sensitizers for focused ultrasound thermotherapy

Desgranges, Stéphane; Lorton, Orane; Gui-Levy, Laura; P, Guillemin; Celicanin, Zarko; Hyacinthe, Jean-Noël; Bréguet, Romain; Crowe, Lindsey A.; Becker, Christoph; Soulié, Marine; Taulier, Nicolas; Contino‐Pépin, Christiane; Salomir, Rarès

doi:10.1039/c8tb01491d

Cited by 13 publications

(24 citation statements)

References 69 publications

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“…This study confirmed the capabilities of PFOB-FTAC micron size droplets to enhance the local absorption of focused ultrasound, as already reported by Desgranges [57]. Differential metrics with and without injection of sonosensitizers showed a significant improvement in the temperature elevation achieved, inducing a dramatic amplification of the thermal dose in the target area.…”

Section: Enhancement Of Hifu Thermal Effect By Liquid-core Micron-sizsupporting

confidence: 90%

“…F-TAC molecules consist of a fluorinated hydrophobic moiety exhibiting a high affinity for PFC droplets and a hydrophilic moiety made of a polyTRIS oligomer as illustrated in Figure 1(a). The surfactant was synthesized in one step by free radical polymerization as previously described [57]. The liquid-core PFOB-FTAC sonosensitizers were prepared using a Polytron homogenizer (model PT3100) from Kinematica (Luzern Switzerland).…”

Section: Sonosensitizersmentioning

confidence: 99%

“…The resulting mixture was cooled down with an ice bath and the resulting emulsion was homogenized three times, each for a duration of 15 min, at 20,000 rpm. Unlike the previous study [57], which encapsulated the micro-droplets in a semi-rigid gel, stable fluid emulsions of sonosensitizers were prepared with 2% v/v of PFOB and purified water. The emulsion was kept at 4 C until use and was stable for at least one month.…”

Section: Sonosensitizersmentioning

confidence: 99%

“…The effect of the enhancement of the HIFU-induced temperature elevation after injection of sonosensitizers was evaluated by defining two metrics similar to [57]. The first metric (units: C/kJ) corresponds to the ratio between the temperature elevation at the focal point when sonication ended (DT max , units C), and the emitted acoustic energy (E, units kJ):…”

Section: Post-processingmentioning

confidence: 99%

“…In a previous study, Desgranges et al [57] reported the use of perfluorooctylbromide (PFOB)-filled micron-sized droplets as a new class of sonosensitizers for enhanced HIFU thermal therapy. PFOB is FDA approved and is used for its high oxygen solubility, low toxicity and short half-life time in the body, making it the best candidate to be used as a contrast agent in human tissues [58].…”

Section: Introductionmentioning

confidence: 99%

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Enhancement of HIFU thermal therapy in perfused tissue models using micron-sized FTAC-stabilized PFOB-core endovascular sonosensitizers

Lorton

Holman

et al. 2020

International Journal of Hyperthermia

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Background: High intensity focused ultrasound (HIFU) is clinically accepted for the treatment of solid tumors but remains challenging in highly perfused tissue due to the heat sink effect. Endovascular liquid-core sonosensitizers have been previously suggested to enhance the thermal energy deposition at the focal area and to lower the near-/far-field heating. We are investigating the therapeutic potential of PFOB-FTAC micro-droplets in a perfused tissue-mimicking model and postmortem excised organs. Method: A custom-made in vitro perfused tissue-mimicking model, freshly excised pig kidneys (n ¼ 3) and liver (n ¼ 1) were perfused and subjected to focused ultrasound generated by an MR-compatible HIFU transducer. PFOB-FTAC sonosensitizers were injected in the perfusion fluid up to 0.235% v/v ratio. Targeting and on-line PRFS thermometry were performed on a 3 T MR scanner. Assessment of the fluid perfusion was performed with pulsed color Doppler in vitro and with dynamic contrastenhanced (DCE)-MRI in excised organs. Results: Our in vitro model of perfused tissue demonstrated re-usability. Sonosensitizer concentration and perfusion rate were tunable in situ. Differential heating under equivalent HIFU sonications demonstrated a dramatic improvement in the thermal deposition due to the sonosensitizers activity. Typically, the energy deposition was multiplied by a factor between 2.5 and 3 in perfused organs after the administration of micro-droplets, while DCE-MRI indicated an effective perfusion. Conclusion: The current PFOB-FTAC micro-droplet sonosensitizers provided a large and sustained enhancement of the HIFU thermal deposition at the focal area, suggesting solutions for less technological constraints, lower risk for the near-/far-field heating. We also report a suitable experimental model for other MRgHIFU studies ARTICLE HISTORY

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Section: Enhancement Of Hifu Thermal Effect By Liquid-core Micron-sizsupporting

confidence: 90%

Section: Sonosensitizersmentioning

confidence: 99%

Section: Sonosensitizersmentioning

confidence: 99%

Section: Post-processingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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