Photodynamic (PDT) and Sonodynamic Therapy (SDT)

For the treatment for cancer using light and ultrasound.

Background

Photodynamic therapy (PDT) is a form of phototherapy using nontoxic light-sensitive drugs (called a photosensitizer, or simply sensitizer for short) that are exposed selectively to light, whereupon they cause targeted malignant and other diseased cells to die.

In a similar way, Sonodynamic therapy (SDT) uses therapeutic ultrasound instead of light to activate these sensitizer compounds, to provide much deeper penetration to the target cancer cells in the body.

Photodynamic therapy (PDT) and Sonodynamic therapy (SDT) may be used individually or as combined therapies depending on the disease, stage of disease, various individual circumstances or other factors which are determined by the doctor and patient. When PDT and SDT are both used for treatment the therapy is sometimes refered to as Sonophotodynamic therapy (SPDT).

sono = (ultra) sound
photo = light

PDT and SDT technology has been developing for a long time all over the world, but some parts are relatively new and the therapy is still evolving. Newer sensitisers are becoming available to target cancer cells in slightly different ways.

Therapy Overview

1. Administration

A light-sensitive and ultrasound-sensitive drug (called a photosensitizer) is administered intravenously, orally or topically onto the skin.
Sensitizers commonly have a chlorophyll or porphyrin ring structure which provides sensitivity to light.
Sensitizers have the characteristic of being preferentially taken up by cancer cells and diseased cells rather than by normal healthy cells.

2. Activation

Photosensitizers are sensitive to specific wavelengths of light and ultrasound sound waves which are absorbed by the sensitizer during the PDT and SDT treatment. In the activation process this light and ultrasound energy breaks molecular oxygen into singlet oxygen and free radicals causing damage to the cancer cells.
Photosensitizers are non-toxic and have minimal side effects.
Treatment can be continued as long as necessary while disease is present in combination with a variety of other modalities, such as GcMAF macrophage activating therapy.

Mechanism of action – Cancer cell death (Necrosis)

Sensitizing agent is selectively incorporated into cancer cells and then irradiated with red light energy and/or ultrasound energy. This causes the breakdown of molecular oxygen into singlet oxygen and free radicals in the cancer cells and leads to cancer cell death (necrosis).

Benefits of PDT and SDT Therapy

Sensitizers are non-toxic and safe to use repeatedly as there is no total dose limitation.
The treatment is targeted to primarily to the tumor with minimal effect on healthy tissue.
PDT and SDT therapy does not suppress immune function. In fact quite the opposite is true. PDT and SDT is a perfect complement to immunotherapies such as GcMAF and Hyper T/NK therapy which enhance immune activity.
Vaccine-like response from immunogenic cancer cell necrosis and cancer-immune response.

Treatment factors and limitations

The depth of light penetration limits the depth of activation.
– Sufficient light needs to reach the tumor in order to activate the breakdown of oxygen which kills the cancer cell.
– The limited depth of penetration of light is overcome by the use of ultrasound sound waves to activate the drug at deeper depths.
Ultrasound is commonly used in medicine because it safely penetrates deep into body tissues
The activation of a sensitizer using ultrasound instead of using light is called Sonodynamic Therapy (SDT).

Sonodynamic Therapy (SDT)

Ultrasound was first found to enhance the treatment effect of chemotherapy drugs in 1976.
Later it was discovered that several photosensitizers are also activated by ultrasound and referred to as a “sonosensitizer”.
Ultrasound creates a mechanical effect on the sonosensitizer which causes:
– Oxygen free radical production
– Sonoporation (physical destabilization of cell membranes)
– Cavitation
Sonodynamic therapy allows deep tumors to be treated and it has the advantage of being non-invasive and targeted because of selective sensitizer uptake by cancer cells.

What’s the evidence for sonodynamic therapy?

Sonodynamic therapy––a review of the synergistic effects of drugs and ultrasound (2004). I Rosenthal, J Sostaric, P Riesz. Ultrasonics Sonochemistry.

Abstract
Sonodynamic therapy, the ultrasound dependent enhancement of cytotoxic activities of certain compounds (sonosensitizers) in studies with cells in vitro and in tumor bearing animals, is reviewed. The attractive features of this modality for cancer treatment emerges from the ability to focus the ultrasound energy on malignancy sites buried deep in tissues and to locally activate a preloaded sonosensitizer. Possible mechanisms of sonodynamic therapy include generation of sonosensitizer derived radicals which initiate chain peroxidation of membrane lipids via peroxyl and/or alkoxyl radicals, the physical destabilization of the cell membrane by the sonosensitizer thereby rendering the cell more susceptible to shear forces or ultrasound enhanced drug transport across the cell membrane (sonoporation). Evidence against the role of singlet oxygen in sonodynamic therapy is discussed. The mechanism of sonodynamic therapy is probably not governed by a universal mechanism, but may be influenced by multiple factors including the nature of the biological model, the sonosensitizer and the ultrasound parameters. The current review emphasizes the effect of ultrasound induced free radicals in sonodynamic therapy.

Safety of sensitizers

Safety studies using a Zebrafish Model (a widely used safety test) have shown an excellent safety profile even at maximal soluble concentrations.
Advice is given to avoid bright sunlight during treatment but no cases of skin sensitivity have been noted.

Tumor hypoxia and Ozone Therapy

Tumors are low in oxygen (hypoxic).
Poor blood oxygenation can reduce the effectiveness of chemotherapy, radiation therapy and photodynamic and sonodynamic therapy.
Ozone autohemotherapy (Ozone Therapy) is performed prior to light and ultrsound activation to increase tumor oxygenation.
Tumor oxygenation was demonstrated to increase following ozone administration in the research.