title: Focused ultrasound induced hyperthermia accelerates and increases the uptake of anti-HER-2 antibodies in a xenograft model.
abstract: Image guided drug delivery has gained significant attention during the last few years. Labelling nanoparticles or macromolecules and monitoring their fate in the body provides information that can be used to modulate their biodistribution and improve their pharmacokinetics. In this study we label antibodies and monitor their distribution in the tumours post intravenous injection. Using Focused Ultrasound (FUS, a non-invasive method of hyperthermia) we increase the tumour temperature to 42°C for a short period of time (3-5min) and we observe an increased accumulation of labelled antibody. Repetition of focused ultrasound induced hyperthermic treatment increased still further the accumulation of the antibodies in the tumour. This treatment also augmented the accumulation of other macromolecules non-specific to the tumour, such as IgG and albumin. These effects may be used to enhance the therapeutic efficiency of antibodies and/or targeted nanoparticles.
authors: Institute of Pharmaceutical Science, King's College London, UK.
authors: Miguel N
authors: MN
authors: Centelles
authors: Institute of Pharmaceutical Science, King's College London, UK.
authors: Michael
authors: M
authors: Wright
authors: Department of Experimental Medicine, Imperial College London, UK.
authors: Wladyslaw
authors: W
authors: Gedroyc
authors: Institute of Pharmaceutical Science, King's College London, UK. Electronic address: maya.thanou@kcl.ac.uk.
authors: Maya
authors: M
authors: Thanou
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D014018:Tissue Distribution; D000068878:Trastuzumab / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: Antibody therapy; Cancer; Focused ultrasound; Herceptin; In vivo imaging; trastuzumab