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.

Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases

“…In a rodent study, the tissue concentration of trastuzumab after systemic administration was undetectable (< 780 ng/g), whereas after sonication, the concentration increased to 3257 ng/g of tissue (45). This significant increase in trastuzumab concentration in tissue using FUS was further corroborated in a xenograft rodent model (70). Notably repeated dose of FUS greatly increased the concentration yield (70).…”

“…This significant increase in trastuzumab concentration in tissue using FUS was further corroborated in a xenograft rodent model (70). Notably repeated dose of FUS greatly increased the concentration yield (70). In another HER2/neu-positive human breast cancer xenograft model, 6 weekly treatment of FUS plus trastuzumab led to what appeared to be complete resolution on MRI (69).…”

“…Human epidermal growth factor 180 receptor 2 (HER2) is addressed when trastuzumab has been administered, and specific inhibition of mutated BRAF, a proto-oncogene is addressed when vemurafenib is administered. Trastuzumab has been found to be highly effective in controlling local and distal breast cancer lesions (45, 69, 70). BRAF inhibitors such as vemurafenib and dabrafenib are effective in extending the progression free survival of BRAF-mutant melanomas which are present in 50% of melanomas and is associated with significantly higher incidence of CNS involvement (71).…”

Ultrasound-mediated microbubble destruction: a new method in cancer immunotherapy

“…To effectively treat brain metastases and reduce side effects, drugs or genes must be delivered efficiently to the brain 70. In the study by Kobus et al, HER2-targeting antibodies combined with US and Optison (GE Healthcare, Milwaukee, WI, USA)™ were utilized to inhibit the growth rate of a tumor model derived from HER2-positive breast cancer metastasis to the brain.…”

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

“…HIFU‐induced short‐duration hyperthermia applied non‐invasively and locally to a malignant tumor can increase the accumulation of active pharmaceuticals, such as antibodies or chemotherapy agents, specifically in the tumor . In some cases, this modality is combined with direct visualization based on fluorescent agents chemically attached to a macromolecule carrier encapsulating the active anticancer agent . This method of increased localized drug delivery therefore opens a range of new highly targeted combinatory treatments for a wide range of cancer indications as well as other medical conditions.…”