Books
in black and white
Main menu
Share a book About us Home
Books
Biology Business Chemistry Computers Culture Economics Fiction Games Guide History Management Mathematical Medicine Mental Fitnes Physics Psychology Scince Sport Technics
Ads

The porphyrin handbook - Kadish K.M.

Kadish K.M. The porphyrin handbook - Academic press, 2000. - 368 p.
Download (direct link): kadishsmishgulilard2000.djvu
Previous << 1 .. 99 100 101 102 103 104 < 105 > 106 107 108 109 110 111 .. 240 >> Next

substitution(s) and coordination of transition-metal ions, porphyrin
systems generally satisfy this criterion.27'75 That is why most of the
sensitizers currently under clinical evaluation for PDT are porphyrins or
porphyrin-based molecules.
It is well established that both absorption and scattering of light by
tissue increases as the wavelength decreases, and that the most efficient
sensitizers are those that have strong absorption bands between 700 and
800 nm.74 Heme proteins in tissue account for most of the absorption of
light in the visible region. Light penetration drops off rapidly beyond
550 nm; however, it doubles from 550 nm to 630 nm (where Photofrin is
activated) and doubles again in going to 700 nm. This is followed by a
10% increase in tissue penetration as the wavelength moves towards 800
nm. The diffusion depth
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
161
700
800
Wavelength (nm)
Figure 2. Relative diffusion depth of penetration with light at various
wavelengths (assuming the depth of tissue penetration at 800 nm is 100%).
of penetration in cells with light of various wavelengths is shown in
Figure 2.77
However, in porphyrin, or reduced-porphyrin systems (chlorins and
bacteriochlorins), a red shift beyond 800 nm is neither desirable
(because of the lack of benefit from deeper tissue penetration) nor
easily achievable. First, if the red shift is related to an extension of
the -system of the heteroaromatic system, the oxidation potential
decreases, and the photosensitizer becomes kinetically less stable and
subject to photobleaching.78 For example, bacteriochloro-phyll a (which
absorbs at 770 nm) is one of the sensitizers which most readily undergoes
photobleaching.79 Secondly, the wavelength often mentioned in the
absorption spectrum refers to the first excited singlet state of the
sensitizer; the energy level of the related triplet state is lower. If
the triplet energy of the sensitizer is lower than 94kJ/mol (1270nm),
efficient energy transfer from the triplet sensitizer to ground-state
triplet oxygen will not be possible; a good example is the 34-71
porphyrin system, which has an absorption band at 970nm, but does not
produce singlet oxygen.80 81
Another reason to set the ideal wavelength to 700-800 nm is the
availability of the light sources in this region. Currently available dye
lasers are expensive and not easy to handle clinically. A better solution
is to use diode lasers. Advantages of diode lasers are low cost,
negligible running
cost, high reliability, small size and portability.82 Although diode
lasers are now available at 630 nm,83 photosensitizers with absorptions
between 700 and 800 nm in conjuction with diode lasers are still
desirable for treating tumors which are deeply seated.
All these factors establish 700-800 nm as the optimal wavelength
absorptions for efficient photosensitizers. Besides the properties
previously discussed, the preferential tumor localization, dark toxicity,
phototoxicity, stability and solubility in appropriate injectable
solvents are other important factors to be considered in developing an
effective PDT agent.
D. ADVANTAGES AND LIMITATIONS OF PHOTOFRIN5484'85
Photofrin, a purified version of HpD (Scheme 1), is the only drug which
has been approved in the United States, Japan, The Netherlands and Canada
for the treatment of various types of cancers. It fits some of the
criteria for ideal sensitizers, but it suffers from several drawbacks.
First, it is a complex mixture of porphyrins with various monomeric and
oligomeric forms. Secondly, its long wavelength absorption falls at 630
nm, which lies well below the wavelength necessary for the maximum tissue
penetration. Finally, it induces prolonged cutaneous photosensitivity, a
major adverse effect associated with this sensitizer. Photofrin chemistry
is summarized briefly in section VIII of this chapter.
II. Porphyrin-based Photosensitizers
A. THEORETICAL CONSIDERATIONS
Porphyrins are 18 -electron aromatic macrocycles that exhibit
characteristic optical spectra with a very strong n-n* transition around
400 nm (Soret band) and usually four Q bands in the visible region. As
can be seen in Figure 3, two of the peripheral double bonds in opposite
pyrrolic rings are
Scheme 1. One of the major components (n = 1) of Photofrin.
R1-V
Me
R = HO-pH- or -CH =CH2 and n = 0-7 R1 = (2)202 Na+
Me
162
Pandey and Zheng
-7

-8
w
-10
-12
Pyrrole N p" Pyrrole N pa ,.'4- ......--
Previous << 1 .. 99 100 101 102 103 104 < 105 > 106 107 108 109 110 111 .. 240 >> Next