Clinical Trial of Sonodynamic Therapy for Glioblastoma Begins in Milan


Key Points

  • Sonodynamic therapy (SDT) uses focused ultrasound to activate agents that selectively accumulate in tumor cells and cause cell death.
  • In this trial, researchers will use SDT in patients with newly diagnosed glioblastomas, a primary malignant brain tumor.  
  • The Foundation is funding this important clinical trial. 

A clinical trial investigating the safety and feasibility of using sonodynamic therapy (SDT) in patients with newly diagnosed glioblastomas (GBMs), a primary malignant brain tumor, has begun enrolling patients at the Fondazione IRCCS Istituto Neurologico Carlo Besta in Milan, Italy.

SDT is an emerging modality for cancer treatment that employs focused ultrasound to interact with an agent to cause cell death only within the tumor. In this pilot trial, researchers will use Insightec’s low-frequency Exablate Neuro focused ultrasound device to activate 5-aminolevulinic acid (5-ALA), an optical imaging agent that accumulates selectively in tumor cells and is commonly used to visualize tumors during surgery.

The study is led by Francesco Prada, MD, neurosurgeon and director of the Acoustic Neuroimaging and Therapy Laboratory at Carlo Besto Neurological Institute. Dr. Prada is also a former Focused Ultrasound Foundation fellow and serves as an advisor to the Foundation’s Brain Program. The Foundation is funding this clinical trial. 

“The study will assess the safety and feasibility as well as the antitumor effects of SDT on patients with newly diagnosed GBMs,” says Dr. Prada. “The low intensity focused ultrasound interacts with 5-ALA to generate cytotoxic compounds and enhance the immune system, thus destroying tumor cells. SDT offers significant advantages and safety because 5-ALA primarily accumulates in tumor cells, while ultrasound energy can be tightly focused and delivered through the intact skull to the targeted area. FUS and 5-ALA separately are not able to create a damage, it is their interaction at the tumor target that is able to induce tumor damage.”

In total, up to 10 patients will receive 5-ALA orally four to six hours before undergoing the focused ultrasound procedure. Then, follow-up scans will be completed at regular intervals to evaluate changes in tumor size. Patients will undergo surgery to remove the tumor approximately two weeks after focused ultrasound, with subsequent chemo- and radiotherapy, which is the traditional treatment method. Patients will then complete a prescribed follow-up of up to three months.

“GBMs are the most common and aggressive primary brain tumors,” explains Dr. Prada. “Patients typically only survive an average of 16 months, even with the best care. We must develop better techniques to battle these tumors, and that is one reason we are targeting GBMs in this initial study. However, if we achieve positive results and the data indicate that SDT is safe, we are hopeful that could pave the way for using SDT in other forms of brain tumors with other sensitizers.”

Similar SDT studies in patients with recurrent GBM are ongoing in the US at the Ivy Brain Tumor Center at Barrow Neurological Institute and St. Joseph’s Hospital and Medical Center in Phoenix, Arizona, and at MD Anderson Cancer Center in Houston, Texas.

To learn more about the Italian clinical trial, please visit

Another Clinical Trial for Patients with GBM
Dr. Prada and his colleagues are also addressing patients with GBM in a separate trial using a different mechanism of focused ultrasound to open the BBB to deliver chemotherapy. Learn more about that study.