Biomedical Engineering Reference
In-Depth Information
Fig. 17.1.
Jablonski diagram for singlet oxygen generation by PDT (Type II pho-
toreaction)
at red/near-infrared wavelength to get good light penetration, high target-to-
nontarget uptake ratio in tissues or cells, and low concentration in the skin
and eyes to avoid complications from accidental light exposure. Photosensi-
tizers that are not water soluble require formulation into liposomes or lipid
emulsions in order to achieve e
cient delivery in vivo. The absorption spectra
of some PDT photosensitizers are shown in Fig. 17.2, together with a plot
showing the general dependence of light penetration in tissues. For example,
HPD has its highest absorption in the UVA/blue region and only a very small
red absorption (at about 630 nm). This contrasts with most second-generation
photosensitizers where the molecule is designed to have the largest absorption
peak above 630 nm where the hemoglobin absorption falls rapidly, but below
about 800 nm in order to maintain high
1
O
2
quantum yield and avoid the NIR
water absorption bands.
One agent that is used widely is aminolevulinic acid (ALA). While not
itself a photosensitizer, administering ALA to cells leads to synthesis of the
photosensitizer protoporphyrin IX (PpIX) [8]. The advantage is that there
is a degree of intrinsic tissue selectivity that does not just rely on enhanced
photosensitizer uptake. ALA-PDT is used in treating tumors, particularly
early-stage, and other indications mentioned above. Its fluorescence has also
made it useful for early cancer/precancer imaging, either for tumor detection
or in guiding tumor surgery, particularly in the brain [9]. As well as selection of
good photosensitizer properties (and enough oxygen), successful PDT requires
that enough light must be delivered to the target tissue to generate biologically
effective levels of
1
O
2
(
>
10
8
molecules per cell). This can be technologically
challenging, since the amount of light required is quite high [10], typically
>
100 J cm
−
2
of red/NIR light incident on the tissue surface. Since this amount
of light has to be delivered in at most tens of minutes for clinical practicality
