Low-Intensity Focused Ultrasound Technique in Glioblastoma Multiforme Treatment.
Authors: Mungur R, Zheng J, Wang B, Chen X, Zhan R, Tong Y
Glioblastoma is one of the central nervous system most aggressive and lethal cancers with poor overall survival rate. Systemic treatment of glioblastoma remains the most challenging aspect due to the low permeability of the blood-brain barrier (BBB) and blood-tumor barrier (BTB), limiting therapeutics extravasation mainly in the core tumor as well as in its surrounding invading areas. It is now possible to overcome these barriers by using low-intensity focused ultrasound (LIFU) together with intravenously administered oscillating microbubbles (MBs). LIFU is a non-invasive technique using converging ultrasound waves which can alter the permeability of BBB/BTB to drug delivery in a specific brain/tumor region. This emerging technique has proven to be both safe and repeatable without causing injury to the brain parenchyma including neurons and other structures. Furthermore, LIFU is also approved by the FDA to treat essential tremors and Parkinson's disease. It is currently under clinical trial in patients suffering from glioblastoma as a drug delivery strategy and liquid biopsy for glioblastoma biomarkers. The use of LIFU+MBs is a step-up in the world of drug delivery, where onco-therapeutics of different molecular sizes and weights can be delivered directly into the brain/tumor parenchyma. Initially, several potent drugs targeting glioblastoma were limited to cross the BBB/BTB; however, using LIFU+MBs, diverse therapeutics showed significantly higher uptake, improved tumor control, and overall survival among different species. Here, we highlight the therapeutic approach of LIFU+MBs mediated drug-delivery in the treatment of glioblastoma.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To review and highlight recent progress in using low-intensity focused ultrasound combined with microbubbles to enhance drug delivery for the treatment of glioblastoma.
Disease model
Glioblastoma
Targeted brain region(s)
Glioblastoma Tumor / Brain (Tumor) Parenchyma
Outcomes and Safety
Summary of Outcomes
Low-intensity focused ultrasound (LIFU) combined with intravenously administered oscillating microbubbles transiently opens the BBB/BTB, increasing delivery and uptake of diverse therapeutics into glioblastoma and surrounding brain, leading to improved tumor control and overall survival across species while remaining safe and repeatable without brain injury. Successful parameter: low-intensity focused ultrasound (LIFU) with intravenous oscillating microbubbles (MBs).
Safety-related matter
The authors state that LIFU+MBs has proven to be safe and repeatable without causing injury to the brain parenchyma (including neurons and other structures), note that LIFU is FDA-approved for other indications, and do not report any adverse effects in this text.
Brain Region
Ultrasound Parameters
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
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