title: Acoustic Cluster Therapy (ACT) - pre-clinical proof of principle for local drug delivery and enhanced uptake.
abstract: Proof of principle for local drug delivery with Acoustic Cluster Therapy (ACT) was demonstrated in a human prostate adenocarcinoma growing in athymic mice, using near infrared (NIR) dyes as model molecules. A dispersion of negatively charged microbubble/positively charged microdroplet clusters are injected i.v., activated within the target pathology by diagnostic ultrasound (US), undergo an ensuing liquid-to-gas phase shift and transiently deposit 20-30μm large bubbles in the microvasculature, occluding blood flow for ~5-10min. Further application of low frequency US induces biomechanical effects that increase the vascular permeability, leading to a locally enhanced extravasation of components from the vascular compartment (e.g., released or co-administered drugs). Results demonstrated deposition of activated bubbles in tumor vasculature. Following ACT treatment, a significant and tumor specific increase in the uptake of a co-administered macromolecular NIR dye was shown. In addition, ACT compound loaded with a lipophilic NIR dye to the microdroplet component was shown to facilitate local release and tumor specific uptake. Whereas the mechanisms behind the observed increased and tumor specific uptake are not fully elucidated, it is demonstrated that the ACT concept can be applied as a versatile technique for targeted drug delivery.
authors.affiliation: Dept. of Physics, NTNU, Trondheim, Norway. Electronic address: annemieke.wamel@ntnu.no.
authors.forename: Annemieke van
authors.initials: AV
authors.lastname: Wamel
authors.affiliation: Phoenix Solutions AS, Oslo, Norway.
authors.forename: Andrew
authors.initials: A
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: Joint Dept. of Physics, ICR, London, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Bush
authors.affiliation: Joint Dept. of Physics, ICR, London, UK.
authors.forename: Jeff
authors.initials: J
authors.lastname: Bamber
authors.affiliation: Dept. of Physics, NTNU, Trondheim, Norway.
authors.forename: Catharina
authors.initials: C
authors.lastname: de Lange Davies
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy; D000818:Animals; D002199:Capillary Permeability / Q000528:radiation effects; D045744:Cell Line, Tumor; D003287:Contrast Media; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D045423:Microbubbles; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy; D019265:Spectroscopy, Near-Infrared; D014465:Ultrasonics / Q000379:methods*
chemical_list: D003287:Contrast Media
keywords: ACT; Acoustic cluster therapy; Local drug delivery; PC-3 prostate adenocarcinoma; Pre-clinical