Photodynamic Therapy - Radiation Damage in Biomolecular Systems - page 454

A need for increased selectivity of photosensitizers for tumour over healthy tissue
clearly appears. A targeted approach employs the utilization of ligands, which can
bind specifically to neovascular endothelium or cellular markers to target tumour.
While antibody-conjugates have received most of the attention [ 72 - 75 ], cellular
transformations offer other potential targets to exploit. Growth factor receptors,
hormonal, insulin, transferrin, glucose, folic acid, and low-density lipoprotein
receptors have been investigated as cellular markers for targeting [ 76 - 79 ]. The
latter, based on the assembly of the photosensitizer with low-density-lipoproteins
(LDL), make LDL as molecular carriers [ 80 ]. This approach is similar to the
encapsulation of photosensitizers within liposomal formulations decorated with
targeting moiety on the surface of liposomes. In this way, the photosensitizer is
not only addressed to the tumour cells, but owing to the large size of carrier,
important amount of photosensitizer molecules can be delivered to a single target
[ 79 , 80 ]. Additionally, the advantage of such carriers is that it can favor the
pharmacokinetics of hydrophobic photosensitizers, which otherwise suffer from
aggregation in the bloodstream, followed by fast clearance from the body. The
rationale for use of molecular delivery systems for photosensitizers is therefore
similar to the delivery of chemotherapeutic drugs. Carrier-mediated delivery allows
increased accumulation of molecule at the target site. Drug delivery approaches
broaden the clinical repertoire of photosensitizers and reduce the precision that is
needed in light delivery.

27.3.3.2 Light sources

With the wide range of clinical applications of PDT, the improvements in PDT light
sources have occurred during the last decades. Light delivery to most anatomic sites
is now achievable.
The basic requirements for light source used in PDT are (i) to cover the
wavelength region of optimal absorption of a given photosensitizer and (ii) to
generate adequate power at this wavelength. Typically, 1-5 W of usable power is
required in the wavelength range 630-850 nm at irradiances of up to several hundred
mW cm 2 so that treatment itself can be less time consuming, i.e. tens of minutes.
Lasers, light emitting diodes (LEDs) and filtered lamps are the three main classes
of PDT light sources used in clinic. The choice of a light source and delivery mode
is usually based on the nature and location of disease. The main issue is, to deliver
enough light from the source to the target tissue.
Depending on accessibility of treated surface, the light can be used directly from
the source with no delivery system; via a lens system; or via a single fibre-optic (e.g.
placed through the instrument channel of an endoscope) with or without a microlens
tip. For intracavitary treatments, the goal is to disperse the light isotropically from
the fibre. In the case of spherical cavities such as resection cavity after surgical
debulking of brain tumours this can be achieved for example by using an inflatable