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This presentation covers the basics of photodynamic therapy (pdt), a light-activated cancer treatment that utilizes photosensitizing agents and light to destroy cancer cells. Learn about the three components required for pdt, how photosensitizers work, and the different ways they can be administered. Discover the mechanisms of cell death and the role of light irradiation in pdt. Explore current research and future directions in this field.
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Rashid Mahmood
Chapter# 12 LIGHT-ACTIVATED
THERAPY: PHOTODYNAMIC THERAPY
Objective
Introduction to PDT
Photsensitizer
Mechanism of cell Death
Light Irradation for PDT
Two Photons PDT
Current Research & Future
Directions
The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed.
Photodynamic therapy or PDT is a treatment that uses special drugs, called photosensitizing agents, along with light to kill cancer cells.The drugs only work after they have been activated or "turned on" by certain kinds of light.
PDT is also called photoradiation therapy, phototherapy.
Three Components are required for PDT
simultaneously:
Photosensitizer
Cellular Oxygen
Light of suitable wavelength
Continued:
Photons
Triplet Drug Oxygen
PDT
Photosensitiser (PS) is administered,
usually by injection or a cream placed on the
skin. After some accumulation time ( in vivo)
light is directed onto the tissue containing
the drug, the drug becomes activated and
destroys the tissue.
How does PDT work?
Photosensitizer (PS) is injected into the body
The tumor is selectively destroyed
The PS concentrates at the tumor sites.
The chemical is activated by the light docsity.com
Contd……….
Type II Reaction:
The photosensitizer in the target tissue is
excited as before to its lowest energy triplet state
and then transfers its excess energy to molecular
oxygen present in the tissue to form a particularly
reactive species called 'singlet oxygen’( amount of
energy, 22 kcal/mol, is required).This excited
oxygen oxidizes and destroys target tissue.
After the transfer of energy, the photosensitizer
returns to its starting point, where it is available
to begin the whole process again.
PHOTOSENSITIZERS (PS)
The compounds having stable electronic configuration and whose ground state is in a singlet state but upon exposure to light , the absorbed photon convert the compound into higher energy state are called photosensitizers.
Photosensitiser is administered, usually by injection or a cream placed on the skin. After some accumulation time light is directed onto the tissue containing the drug, the drug becomes activated and destroys the tissue
PROPERTIES OF AN IDEAL PS
The first group of photosensitizers used in clinical PDT were hematoporphyrin derivatives. Photofrin® is a di-acid and is composed of differing fractions of oligomers (85%) ,porphyrin monomers and dimers, which are required for successful therapy [31-32]. Its chemical formula is C68H74N8 O11 ,with molecular weight of 1179. g/mol.
From figure 2 it is clear that absorption peaks lies between 400~650 nm and all the Porphyrines exhibits weak absorption maxima around 630 nm.
Benzoporphyrins are fused-ring chlorin derivatives produced by cyclo-addition reactions. The mono-acid benzoporphyrin derivative, called veteroporfin (also labeled BPD-MA), absorbs at 690nm. PDT trials of this photosensitizer show rapid tumor accumulation and reduced skin photosensitivity. A benzoporphyrin derivative has been approved for the treatment of age-related macular degeneration (ARMD).
Advantage over Photofrin® is rapid clearance which is more desirable in PDT.
Another interesting photosensitizer is aminolaevulinic acid which itself is not even a photosensitizer but a precursor of the endogeneous synthesis of porphyrins. According to Q.Ping at el naturally occurring amino acid is converted enzymatically to protoporphyrin. The drug is active at 630 nm, which is adequate for the maximal absorption of ALA. ALA is not highly active, therefore relatively high light energy or long treatments are needed.
Figure 3 Molecular structure for ALA.