Focused ultrasound for opening blood-brain barrier and drug delivery monitored with positron emission tomography.
Authors: Arif WM, Elsinga PH, Gasca-Salas C, Versluis M, Martínez-Fernández R, Dierckx RAJO, Borra RJH, Luurtsema G
Focused ultrasound (FUS) is a minimally-invasive technology used for treatment of many diseases, including diseases related to the colon, uterus, prostate, and brain. Although it has been mainly used for ablative procedures, the ability of FUS to open the blood-brain barrier (BBB) presents a promising new application. However, the mechanism of BBB opening by FUS remains unclear. This review focuses on the use of FUS to open the BBB for enhancing drug delivery and investigating how Positron Emission Tomography (PET) provides insight into the underlying mechanism.
Introduction
Purpose
drug delivery with BBB opening
Outcomes and Safety
Summary of Outcomes
This review summarizes the use of focused ultrasound (FUS) with microbubbles to reversibly open the blood-brain barrier (BBB) for enhanced drug delivery, and highlights the role of positron emission tomography (PET) in monitoring BBB opening and transporter function. Preclinical studies have demonstrated FUS-mediated delivery of radiotracers such as [³-¹¹C]AIB, [¹⁸F]FBPA-Fr, [⁶⁸Ga]bevacizumab, and ⁶⁴Cu-labeled gold nanoclusters. FUS can also transiently inhibit P-glycoprotein (P-gp) and alter GLUT-1 expression, as assessed with PET tracers like [¹¹C]erlotinib, [¹⁸F]MC225, and [¹⁸F]FDG. Clinical studies in Alzheimer's disease, ALS, and brain tumors show safety and feasibility. The review discusses optimal FUS parameters (frequency 0.3-1.5 MHz, pressure 240-810 kPa, burst length 10 ms, PRF 1 Hz, duration 60-120 s) and emphasizes the need for further PET studies to understand BBB transport mechanisms
Brain Region
Targeted brain region(s)
Not specified
Ultrasound Parameters
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