Pitt Shield

Identifying new therapeutics for focused ultrasound-enhanced drug delivery in the management of glioblastoma.

Authors: Holman R, McDannold N

Glioblastoma, a grade IV astrocytoma, typically has a poor prognosis, with most patients succumbing within eighteen months of diagnosis and few experiencing long-term survival. Focused ultrasound, an emerging localized therapy, has shown promising results in early-phase studies for glioblastoma by improving the uptake of temozolomide and carboplatin. The blood-brain barrier is critical to homeostasis by regulating the movement of substances between the bloodstream and the central nervous system. While this barrier helps prevent infections from bloodborne pathogens, it also hinders the delivery of cancer therapies to gliomas. Combining focused ultrasound with circulating microbubbles enhances local blood-brain barrier permeability, facilitating the intratumoral uptake of systemic cancer therapies. The purpose of this study was to identify promising new therapeutics in the treatment of glioblastoma for localized drug delivery via focused ultrasound. This review provides an overview of the current standard of care for newly diagnosed and recurrent glioblastoma, identifies current therapies indicated for the treatment, discusses key aspects of microbubble resonators, describes focused ultrasound devices under evaluation in human trials, and concludes with a perspective of emerging therapeutics for future studies.

Introduction

Purpose Drug delivery with BBB opening
Study Objective To identify promising new therapeutics for treating glioblastoma that could be delivered locally via focused ultrasound.
Animal model / Human subject Not reported
Disease model Glioblastoma
MRI or image guidance method MRI
Targeted brain region(s) Glioblastoma (Intratumoral Region / Blood–Brain Barrier At The Tumor Site)
Target coordinates Not provided
Cargo name and characteristics Temozolomide — small-molecule alkylating chemotherapeutic; Carboplatin — small-molecule platinum-based chemotherapeutic
Route of administration Intravenous (systemic delivery with circulating microbubbles and focused ultrasound to open the blood-brain barrier)

Outcomes and Safety

Summary of Outcomes Focused ultrasound combined with circulating microbubbles transiently disrupts the blood-brain barrier to enhance intratumoral uptake of systemic therapies, demonstrating safety, tolerability, and preliminary efficacy in glioblastoma models and early clinical studies.
Duration of biological effect eighteen months
Safety-related matter The paper states that most studies were aimed at establishing safety and feasibility and that FUS-enhanced delivery has demonstrated safety and tolerability in preclinical and early-phase clinical studies.

Brain Region

Ultrasound Parameters

Ultrasound instrument (InSightec, Haifa, Israel), (NaviFUS Corp., Taipei, Taiwan), (CarThera, Paris, Île-de-France, France)
FUS Frequency 500 kHz, 220 kHz, 1 MHz
FUS Intensity Not reported
FUS Pressure Not reported
FUS Mode pulsed
Pulse duration Not reported
Duration of a single FUS session Not reported in the provided text.
Focal Characteristics Not reported
Treatment frequency not specified

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