Photodynamic Therapy

Presented By, Ishaque PK Dept. of Biochemistry & Molecular Biology Pondicherry University

Contents…• Synonyms.• What is photodynamic therapy?• How is PDT used to treat cancer?• Photosensitizers.• Mechanism behind the PDT.• What types of drugs and cancer are

currently treated with PDT?• Advantages.• complications or side effects?• Future hold for PDT.• References.

Synonyms…• Photoradiation therapy, • Phototherapy, • Photochemotherapy.

What is photodynamic therapy?

• Photodynamic therapy (PDT) is a treatment that uses a drug, called a photosensitizer or photosensitizing agent.

• Photosensitizers are exposed to a specific wavelength of light, photoactivation causes the formation of singlet oxygen, which produces peroxidative reactions that can cause cell damage and death.

PDT essentially has three steps :– Application of photosensitizer drug.– Incubation.– Light activation.

• First, a light sensitizing liquid, cream, or intravenous drug (photosensitizer) is applied or administered.

• Second, there is an incubation period of minutes to days.

• Finally, the target tissue is then exposed to a specific wavelength of light that then activates the photosensitizing medication.

How is PDT used to treat cancer?

• A wide array of photosensitizers for PDT exist.• Some examples include:

aminolevulinic acid (ALA), Silicon Phthalocyanine Pc 4, 

m-tetrahydroxyphenylchlorin (mTHPC), mono-L-aspartyl- chlorin e6 (NPe6), Benzoporphyrin derivative ,etc.

• Several photosensitizers are commercially available for clinical use, such as: Allumera, Photofrin, Visudyne, Levulan, Foscan, Met

vix, Hexvix, Cysview, and Laserphyrin,etc.

• with others in development, e.g. Antrin, Photochlor, Photosens, Photrex, Lumaca

n, Cevira, Visonac, BF-200-ALA. Amphinex. Also Azadipyrromethenes.

Photosensitizers…

• The light used for PDT include laser.

• Laser light can be directed through fiber optic cables (thin fibers that transmit light) to deliver light to areas inside the body.

• Other light sources include intense pulsed light, light-emitting diodes (LEDs), blue light, red light, and many other visible lights (including natural sunlight). 

Mechanism behind the PDT…

•Photodynamic activation of macrophage like cells contributes to an effective outcome of PDT treatment. The possibility for an enhancement of macrophage activity by photosensitization with meta-tetra(hydroxyphenyl)chlorin (mTHPC) (1 μg ml–1) was studied, monocyte cell line differentiated into macrophages.

•Pyropheophorbide-a methylester (PPME) is a photosensitizers, photosensitization triggered apoptosis of colon cancer cells via DNA laddering, PARP cleavage, caspase activation and mitochondrial release of cytochrome c.

•2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) to induce proinflammatory cytokines and chemokines, as well as adhesion molecules, known to be involved in neutrophil migration, results in the rapid induction of an inflammatory response that is considered important for the activation of antitumour immunity.•Foscan® (mTHPC) photosensitized macrophage activation: enhancement of phagocytosis, nitric oxide release and tumour necrosis factor--mediated cytolytic activity,British Journal of Cancer Research Article (01 Sep 1999).

•Nitric oxide production by tumour tissue: impact on the response to photodynamic therapy,British Journal of Cancer Research Article (01 Jun 2000).

•Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization Oncogene, Original Article (06 Jul 2001).

•Role of cytokines in photodynamic therapy-induced local and systemic inflammation,British Journal of Cancer Original Article (02 Jun 2003).

What types of drugs and cancer are currently treated with PDT?

• Porfimer sodium, BPD verteporfin - Cancer of the esophagus (the swallowing tube), Barrett esophagus (a pre-cancerous condition that may lead to esophageal cancer), non-small cell lung cancer or endobronchial cancer.

• Aminolevulinic acid (ALA or Levulan), Methyl ester of ALA (Metvixia® cream) - actinic keratosis (AK).

• Pyropheophorbide-a methylester (PPME) - colon cancer.

Advantages…It has some advantages, such as:• It has no long term side effects when used

properly.• It’s less invasive than surgery. • It usually takes only a short time and is most often

done as an outpatient.• It can be targeted very precisely.• Unlike radiation, PDT can be repeated many times

at the same site if needed.• There’s little or no scarring after the site heals.• It often costs less than other cancer treatments.• PDT is currently used in a number of medical

fields, including oncology (cancer), dermatology (skin), and cosmetic surgery.

What are the limitations of PDT?• The light needed to activate most

photosensitizers cannot pass through more than about one third of an inch of tissue (1 centimeter).

• For this reason, PDT is usually used to treat tumors on or just under the skin or on the lining of internal organs or cavities.

• PDT is also less effective in treating other tumors, because the light cannot pass far into these tumors.

• PDT is a local treatment and generally cannot be used to treat cancer that has spread (metastasized).

complications or side effects?• Drugs makes the skin and eyes sensitive to

light for approximately 6 weeks after treatment.(Thus, patients are advised to avoid direct sunlight and bright indoor light for at least 6 weeks.)

• Photosensitizers tend to build up in tumors and the activating light is focused on the tumor. As a result, damage to healthy tissue is minimal.

• However, PDT can cause burns, swelling, pain, and scarring in nearby healthy tissue.

• Other side effects include coughing, painful breathing, trouble swallowing, stomach pain, or shortness of breath; these side effects are usually temporary.

Future hold for PDT…• Researchers continue to study ways to improve

the effectiveness of PDT and expand it to other cancers. 

• Clinical trials (research studies) are under way to evaluate the use of PDT for cancers of the brain, skin, prostate, cervix, and peritoneal cavity (the space in the abdomen that contains the intestines, stomach, and liver).

• Other research is focused on the development of Photosensitizers that are more powerful, more specifically target cancer cells, and are activated by light that can penetrate tissue and treat deep or large tumors.

• Researchers are also investigating ways to improve equipment and the delivery of the activating light.

References…• Dolmans DE, Fukumura D, Jain RK. Photodynamic

therapy for cancer. Nature Reviews Cancer 2003; 3(5):380–387.

• Wilson BC. Photodynamic therapy for cancer: principles. Canadian Journal of Gastroenterology 2002; 16(6):393–396.

• Vrouenraets MB, Visser GW, Snow GB, van Dongen GA. Basic principles, applications in oncology and improved selectivity of photodynamic therapy. Anticancer Research 2003; 23(1B):505–522.

• Wei Li, Qingyong Ma, and Erxi Wu. Perspectives on the Role of Photodynamic Therapy in the Treatment of Pancreatic Cancer. Received 15 May 2011; Revised 25 July 2011; Accepted 1 August 2011.