Photodynamic Therapy (PDT): A new light to Cancer Therapy

Photodynamic Therapy (PDT): A new light to Cancer Therapy

Prof .Tariq Sainuddin

Research and Teaching Assistant

Acadia University, Canada.

 

The incidence of cancer patients is rising in India, according to the WHO it is estimated 5 lakh Indians died in 2010 and this trend will set to increase to 7 lakh annually by 2015. Although platinum-based compounds such as Cisplatin, Carboplatin and Oxaplatin are used for treating 50-70% of cancer patients, the main problem is its non-specificity and high toxicity to normal body cells leading to nephrotoxicity, severe peripheral nerve damage and suppression of bone marrow activity. Therefore an efficient, safe and cost effective treatment method has to be introduced apart from radiation, chemotherapy, and surgery.

PDT is an alternative cancer treatment modality that utilizes light, photosensitiser (PS) and oxygen. PDT is done in stages an injected PS is allowed to distribute throughout the body (5 min-48hrs) and then a light of specific wavelength directed at the tumour to activate the PS (figure 1). This activated PS result in the production of either free radicals like reactive oxygen species (Type I mechanism) or highly reactive singlet oxygen (Type II mechanism). Consequently, either apoptosis or necrosis of the tumour cells occurs. PS can also damage the vasculature that supplies nutrients to the tumour. It should be noted that current PDT works via Type II mechanism so molecular oxygen is a very important component for therapy. Here are some clinically approved photosensitisers which are listed along with their uses and wavelength of absorption and light and drug dose (Table 1).

Generic Name	Brand Name	Uses	Wavelength of activation, light dose & drug dose
Porfimer Sodium* (i.v)	Photofrin® Photogem®	Esophageal cancer, endobronchial cancer, bladder cancer, Barrett’s Esophagus	630nm 130,200 or 300J/cm2 2mg/kg
Amino levulinic acid (topical)	Levulan®	Actinic keratosis	400-450 nm (topical)
Temoporfin (i.v)	Foscan®	Squamous cell carcinoma of the head and neck	652 nm 0.15mg/kg 20 J/cm2
HPPH (i.v)	Photochlor®	Barrett’s esophagus. cutaneous lesions, including basal cell cancer	665nm 150, 175 or 200 J/cm2  3 to 6 mg/m2
Verteporfin (i.v)	Visudyne®	Age-related macular degeneration(AMD), pathologic myopia, ocular histoplasmosis	693nm  < 150 J/cm2 6 mg/m2

Table 1: Clinically approved PS with its uses, wavelength of activation, light and drug dose.

*Porfimer sodium (Photofrin) is the first clinically approved photodynamic drug in 1993 in Canada

Light is very critical for effective treatment; parameters like light intensity, spectral wavelength and time of exposure is important for PDT in order to avoid unwanted tissue damage Most light sources include Laser, LEDs, Xenon Lamp, Halogen Lamp, Laser Diodes and Fibre optics. Usually these light sources are custom made from the respective manufactures that produces PS.  Activation of PS at visible light wavelength (700-800nm) is beneficial because of its limited light penetration and localized illumination, which reduces harm to healthy tissue. This counts a big advantage over radiation therapy which is highly penetrative and damages normal tissue cells.

Molecular oxygen is the other essential component for PDT in order to produce the highly reactive singlet oxygen in order to damage the DNA, lipid membrane or blood vessels that supply nutrients. The fact is most PS act via type II mechanism (singlet oxygen production) rather than type I mechanism (free radical or reactive oxygen species generation). But in some cases oxygen shortages occur in the inner regions of cancer cell. This hypoxic condition of tumour cells especially for late cancer treatment can lead to ineffective PDT therapy.

Challenges & Future Scope

In PDT many variables come to play such as individual’s metabolism of PS, light penetration and drug delivery. Other factors include size, shape and morphology of the tumor. These concerns can be mitigated only through experience and by making changes to clinical PDT treatment protocol. An optimized treatment method can be used in the process for better PDT treatment. Recent research on PDT are focussed on finding new photosensitisers with improved drug delivery for resolving solubility issues and specific targeting by tethering PS with a nanoparticle or antibodies.

Info to Pharmacist

After treatment, PDT patients are strictly advised to avoid direct exposure to light. This is necessary for the first 48hrs, and then reduced light exposure for at least 4 weeks to ensure the complete clearance of the PS.  Patients are also advised to wear long-sleeved shirt, full pants, gloves, socks, shoes, sunglasses and wide-brimmed hat. It should be noted that use of sunscreens cannot provide protection against photosensitivity caused due to these medications. Proper storage of these medications is crucial, normally they are kept at room temperature and protected from light due to the phenomenon called photo bleaching.