Photodynamic Therapy with Porphyrins

Copyright © 1995–97
by Mike P. Gagel, RN, MSN

Overview of Photodynamic Therapy

PHOTODYNAMIC THERAPY (PDT) is the combination of light and light sensitive agents (such as porphyrins) in an oxygen-rich environment. Porphyrins are a component of hemoglobin, which in turn is a component of red blood cells. Hemoglobin is what carries oxygen in the blood. When porphyrins are not used as a component of hemoglobin, they can absorb energy from photons (particles of light) and transfer this energy to surrounding oxygen molecules. Toxic oxygen species such as singlet oxygen and free radicals are thus formed. These chemicals are very reactive and can damage proteins, lipids, nucleic acids and other cellular components. Just as chlorophyll in plants utilizes energy from sunlight to produce sugar, porphyrins utilize energy from light to produce toxic oxygen species.
      Modern PDT originated at the turn of the century in Germany. Researchers experimenting with self-injection of porphyrins noted sunburns due to PDT reactions in their skin. Derived from animal hemoglobin, two forms of porphyrin are well known: hematoporphyrin derivative (HPD) and porfimer sodium (Photofrin®). Photofrin® is in Phase III clinical trials and has received approval in Canada for use with bladder carcinoma where treatment with BCG vaccine has failed. (Photofrin® has been approved in other countries for treatment of esophageal cancer and lung cancer.) These first generation photosensitizers display prolonged and generalized photosensitivity of the skin as their primary side effect. Second generation photosensitizers exhibit far less photosensitization and are now in early clinical trials (one example is BPD verteporfin). BPD verteporfin was recently in Phase I/II clinical trials for:

• primary skin carcinoma
• cutaneous lesions where cancer has metastasized to the skin, and
• chronic stable plaque psoriasis.

We are currently evaluating BPD verteporfin in Vancouver, BC, Canada for treatment of chronic stable plaque psorasis in patients who also have psoriatic arthritis.

      Lasers are the primary light source for activation of porphyrins because laser light is monochromatic (exactly one colour), coherent (light waves are parallel permitting precise focusing), and intense (allowing for shorter treatment times). Light Emitting Diodes (LEDs) and florescent light sources are now being used as alternative light sources as they are more convenient than lasers but do result in longer treatment times.

Go to: Clinical Trials, Typical PDT, Photofrin®, BPD, Vancouver Trials, QLT

Clinical Trials

Clinical trials are drug studies. There are four phases of clinical trials:

• Phase I – laboratory and animal studies leading to a few studies with human volunteers to determine a drug's safety (e.g., establish side effects, how the body uses the drug, how the drug circulates, how it is excreted).
• Phase II – once safety is established, more testing is done to determine a drug's effectiveness (i.e., how best to use the drug).
• Phase III – comparison with standard treatments.
• Phase IV – combination with standard treatments (to determine if superior results can be obtained).

Go to: Overview PDT, Typical PDT, Photofrin®, BPD, Vancouver Trials, QLT

A typical PDT session

• Intravenous injection (I.V.) or topical application of a photosynthesizing agent such as a porphyrin.
• Permit time for systemic porphyrins (I.V. injection) to be cleared from normal tissues and be preferentially retained by rapidly growing tissues (e.g., cancer or psoriasis), or for topical porphyrins to be absorbed by the skin.
• Application of light to provide the catalyst for chemical reactions.
• Generation of toxic oxygen species in illuminated tissues.
• Tissue damage usually resulting from damage to vasculature.

Go to: Overview PDT, Photofrin®, BPD, Vancouver Trials, QLT

Photofrin®

• Manufactured by QLT Phototherapeutics.
• In clinical trials for the past decade.
• First PDT agent to receive regulatory approval.
• I.V. injection and then light application within a 48–72 hour period (to allow for clearing of Photofrin® from normal tissue).
• Red light (630 nm wavelength) activation.
• Major side effect is generalized photosensitivity lasting up to 6–8 weeks following I.V. injection.

Go to: Overview PDT, Typical PDT, BPD, Vancouver Trials, QLT

BPD verteporfin

Our current Psoriasis/Psoriatic Arthritis Trial is full. Please call +1 (604) 875-5254 for more information. (Posted 15Apr97.)

• Manufactured by QLT Phototherapeutics.
• In clinical trials since 1992.
• I.V. injection and then light application within a 1.5–6 hour period (advantage over Photofrin®).
• Activated by red or ultraviolet A (UVA) light.
  • Red light (690 nm wavelength) activation (advantage over Photofrin® when treating cutaneous cancers as this wavelength of light penetrates tissue more deeply than 630 nm light).
  • UVA light (290–320 nm wavelength) activation (able to use commonly available light sources, e.g., Psoriasis Clinic light booths).
• Major side effect is generalized photosensitivity lasting up to 3–4 days (advantage over Photofrin®).
• Photobleaching of residual BPD verteporfin in the presence of normal light levels (Photofrin® patients initially stay in darkened rooms).
• Promising results with skin cancer (, et al. in press), and psoriasis (Hruza, L., et al. in press).

Go to: Overview PDT, Typical PDT, Photofrin®, Vancouver Trials, QLT

Vancouver Trials:

Our current Psoriasis/Psoriatic Arthritis Trial is full (16Apr97). For more information please call:

Click here for Q&As from our Psoriasis Studies.

Go to: Overview PDT, Typical PDT, Photofrin®, BPD, QLT

For information on Photofrin® or BPD verteporfin, contact:

Go to: Overview PDT, Typical PDT, Photofrin®, BPD, Vancouver Trials

Created: 06Dec95. Revised: 16Apr97.

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