Sonodynamic therapy and magnetic resonance-guided focused ultrasound: new therapeutic strategy in glioblastoma

Abstract

Glioblastoma (GB) is one of the most aggressive and difficult-to-treat brain tumors, with a poor prognosis and limited treatment options. In recent years, sonodynamic therapy (SDT) and magnetic resonance focused ultrasound (MRgFUS) have emerged as promising approaches for the treatment of GB. SDT uses ultrasound waves in combination with a sonosensitizer to selectively damage cancer cells, while MRgFUS delivers high-intensity ultrasound waves to precisely target tumor tissue and disrupt the blood–brain barrier to enhance drug delivery. In this review, we explore the potential of SDT as a novel therapeutic strategy for GB. We discuss the principles of SDT, its mechanisms of action, and the preclinical and clinical studies that have investigated its use in Gliomas. We also highlight the challenges, the limitations, and the future perspectives of SDT. Overall, SDT and MRgFUS hold promise as novel and potentially complementary treatment modalities for GB. Further research is needed to optimize their parameters and determine their safety and efficacy in humans, but their potential for selective and targeted tumor destruction makes them an exciting area of investigation in the field of brain cancer therapy.

Beyond fluorescence-guided resection: 5-ALA-based glioblastoma therapies

“…In several in vitro studies, efficacy of SDT was demonstrated via apoptotic effects and generation of ROS. Similar results have been shown by in vivo studies in animal models [ 4 , 24 , 33 , 38 , 39 ].…”

“…The duration of the intervention was 10 ms to 20 min. According to the known photosensitizers used for PDT, the following sonosensitizers have been analyzed: 5-ALA, fluorescein (FL), sinoporphyrin sodium (DVDMS), hematoporphyrin monomethyl ether (HMME), temozolomide (TMZ), and Photofrin [ 4 ]. Among these, 5-ALA is the most extensively studied sonosensitizer whose biocompatibility and biosafety have been widely demonstrated in clinical studies [ 7 ].…”

Glioblastoma Therapy: Past, Present and Future

“…The porcine model allows a more precise target definition, and better approaches human conditions [ 1058 ]. The efficacy of STD is limited in larger tumors because ultrasound waves cannot penetrate deep enough into the tumor [ 1059 ]. Three clinical trials are currently underway to evaluate the safety and feasibility of SDT with 5-ALA in patients with high-grade glioma (NCT04559685), in ndGBs using the ExAblate Model 4000 Type-2 Neuro System (NCT04845919), and the efficacy of SDT using SONALA-001 and Exablate Type-2 devices in subjects with rGB (NCT04988750).…”

Focused ultrasound as a treatment modality for gliomas

“…SDT combines focused ultrasound with sonosensitizers, which sensitize cells to sound-induced destruction, minimizing adverse events and maximizing target responses ( 48 , 55 ). Examples of sonosensitizers include 5-ALA, ATX-70, and Hypocrellin ( 56–58 ). The efficacy of SDT has been shown in studies by Sheehan et al, which demonstrated SDT’s efficacy in rat C6 and human U87 glioma cells by showing FUS and 5-ALA-induced cell death through ROS generation ( 59 ).…”

“…As a result, other studies have investigated the possibility of combining LIFUS with BBB modifiers, such as microbubbles, to increase the permeability of the BBB and improve SDT efficacy ( 64–66 ). Sonosensitizers used in Sonodynamic Therapy (SDT) comprise benign molecules that induce cytotoxic effects under an acoustic field ( 56 ). Several of these molecules are similar to those used in photodynamic therapy and are usually porphyrin-based or related compounds such as protoporphyrin IX and hematoporphyrin, among others.…”