Sonodynamic Therapy: Sounding Out a New Frontier in Medicine

Posted on | by Brian Roden

Sonodynamic therapy (SDT) is a minimally invasive treatment that uses ultrasound waves to activate a chemical agent called a sonosensitizer. The sonosensitizer produces reactive oxygen species (ROS), which damage and kill target cells.

Understanding Sonodynamic Therapy

The science behind SDT is based on the principle that ultrasound waves can create acoustic cavitation bubbles in tissues. Acoustic cavitation is the formation of bubbles in a liquid when subjected to high-intensity sound waves. These bubbles can collapse violently, generating high energy levels estimated to be ~100 microjoules per bubble. That energy is sufficient to break a chemical bond or damage cellular tissue. It is important to note that not all of this energy is released in a single burst. The energy is released over a short time, and it can be spread out over a large area.

When a sonosensitizer is present in the tissue, it can be activated by the acoustic cavitation bubbles. This activation produces ROS, highly reactive molecules that can damage DNA and other cellular components. Examples of ROS include:

  • Superoxide anion (O2•-)
  • Hydrogen peroxide (H2O2)
  • Hydroxyl radical (•OH)
  • Singlet oxygen (1O2)
  • Nitric oxide (NO)
  • Peroxynitrite (ONOO-)

Several sonosensitizers have been developed. Many are based on porphyrin molecules, the basic structure of the oxygen-carrying component of the red blood cell in humans. A brief list of sonosensitizers that are being evaluated are:

  1. Hematoporphyrin derivative (HPD): This is a naturally occurring porphyrin consisting of a complex mixture of porphyrins derived from hematoporphyrin, a compound found in blood. HPD is taken up by tumor cells more than by normal cells. When HPD is exposed to ultrasound, it produces free radicals, which can damage tumor cells. HPD is injected into the bloodstream and is then distributed throughout the body. It takes about 48 hours for HPD to reach its maximum concentration in the tumor cells.
  2. Photofrin II: Photofrin is a chemically modified form of HPD. It is more photostable and water-soluble, allowing it to be more effectively distributed when administered. Like HPD, Photofrin II is injected into the bloodstream and distributed throughout the body. It takes about 24 hours for Photofrin II to reach its maximum concentration in the tumor cells. The tumor cells are then exposed to ultrasound. This activates the Photofrin II, causing it to produce free radicals, which damage the tumor cells, leading to their death.
  3. ATX-70: Although no longer in development, ATX-70 is an example of a class of compounds being investigated for SDT. They are gallium porphyrin complexes. Essentially, the iron atom in the HPD complex is replaced by gallium. It is more photostable and water-soluble than HPD itself or Photofrin II. ATX-70 is injected into the bloodstream and is then distributed throughout the body. It takes about 24 hours for ATX-70 to reach its maximum concentration in the tumor cells. The tumor cells are then exposed to ultrasound waves. The ultrasound waves activate the ATX-70, causing it to produce free radicals. The free radicals damage the tumor cells, leading to their death.
  4. A7X–S10: This is a molecule under development by Avicenna Medical for the treatment of liver cancer and breast cancer. A7X-S10 is a chlorin derivative. It is more photostable and water-soluble than HPD and Photofrin II. Early studies show it effectively kills cancer cells in vitro and in vivo. They also indicate the compound to be safe and well-tolerated by patients. However, A7X-S10 is in early Phase 1/2 recruitment for multiple indications. Additional data is needed to determine its overall efficacy.
  5. DCPH-P-Na (I): DCPP-P-Na (I) was developed by a team of researchers at the University of Tokyo in Japan. It has been studied primarily in animal models and has exhibited in vitro and in vivo activity against cancer cells. The safety profile in animal studies is good, but this does not always translate well into human models. The compound can be selectively targeted to tumor cells, which minimizes the risk to healthy tissue. Although promising, additional studies are needed to determine long-term safety and efficacy in humans.

Use of SDT in Medical Applications

SDT is a relatively new treatment. There are distinct advantages to SDT. It is a minimally invasive treatment that has minimal side effects itself. Sound waves can treat deep-seated cancers, infections, and surface afflictions such as acne or psoriasis.

Limitations of the therapy are targeted delivery of the sonosensitizer and specific targeting of the ultrasound energy. Some minor side effects are reported, including pain and swelling in the treatment area. The therapy is also limited to facilities that have targeted ultrasound devices.

Listed below is a summary of studies evaluating SDT in a variety of therapeutic areas:

  1. Cancer treatment: One of the most promising areas of investigation is SDT in treating various cancers. Specifically:
    • Breast cancer (NCT04918553, UCSF)
    • Liver cancer (NCT05142903, University of Pennsylvania)
    • Pancreatic cancer (NCT04853743, University of Pittsburgh)
    • Head/neck cancer (NCT04956757, University of Texas)
    • Glioblastoma (NCT05370508, SonALAsense (a GreenField Partner).
  2. Infection treatment: SDT is being investigated for the treatment of infections a variety of infection types:
    • Bacterial infections (NCT05179648, UC San Diego) and (NCT05503602, UCLA)
    • Fungal infections (NCT05320734, University of Pittsburgh)
    • Viral infections (NCT05390967, University of Texas)
    • Acne vulgaris (NCT05546310, UC, Davis)
  3. Tissue repair: SDT is being investigated for treating tissue damage, such as burns and wounds.
    • Diabetic foot ulcers (NCT04714036, UC, Irvine)
    • Psoriasis (NCT04778645, UCSF)
    • Osteoarthritis (NCT04806164, UC, San Diego)
    • Dupuytren’s contracture, a condition that causes the fingers to contract (NCT04905853, University of Pittsburgh)

SDT is a promising new treatment that can improve the lives of many patients across many therapeutic areas. As research continues, SDT will likely become a more widely used treatment.

Greenfield is proud to be a part of developing this promising new therapy!

(NOTE: If you want to participate in a clinical trial using SDT, you can talk to your doctor. They can help you find a clinical trial that is right for you. It is important to note that clinical trials are research studies and do not guarantee treatment. Before participating in a clinical trial, it is important to talk to a medical professional about the risks and benefits of the study.)