title: Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics.
abstract: Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-μm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 μm, with no bubbles >44 μm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers.
authors.affiliation: Phoenix Solutions AS, Oslo, Norway. Electronic address: Andrew.healey@phoenixsolutions.no.
authors.forename: Andrew John
authors.initials: AJ
authors.lastname: Healey
authors.affiliation: Phoenix Solutions AS, Oslo, Norway.
authors.forename: Per Christian
authors.initials: PC
authors.lastname: Sontum
authors.affiliation: Phoenix Solutions AS, Oslo, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Kvåle
authors.affiliation: University of Oslo, Oslo, Norway.
authors.forename: Morten
authors.initials: M
authors.lastname: Eriksen
authors.affiliation: Medistim ASA, Oslo, Norway.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Bendiksen
authors.affiliation: Ultimovacs AS, Oslo, Norway.
authors.forename: Audun
authors.initials: A
authors.lastname: Tornes
authors.affiliation: Inven2 AS, Oslo, Norway.
authors.forename: Jonny
authors.initials: J
authors.lastname: Østensen
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis; D003287:Contrast Media / Q000737:chemistry / Q000528:radiation effects; D003692:Delayed-Action Preparations; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D005290:Ferric Compounds / Q000097:blood / Q000737:chemistry* / Q000528:radiation effects*; D005740:Gases / Q000138:chemical synthesis / Q000528:radiation effects; D019220:High-Energy Shock Waves; D007501:Iron / Q000097:blood / Q000737:chemistry* / Q000528:radiation effects*; D008297:Male; D010087:Oxides / Q000097:blood / Q000737:chemistry* / Q000528:radiation effects*; D010316:Particle Size; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*
chemical_list: D003287:Contrast Media; D003692:Delayed-Action Preparations; D005290:Ferric Compounds; D005740:Gases; D010087:Oxides; C069727:Sonazoid; D007501:Iron
keywords: Acoustic cluster therapy; Droplet vaporization; Ex vivo bubble sizing; In vitro bubble sizing; In vivo bubble sizing; Microbubbles; Myocardial perfusion imaging; Ultrasound contrast agent