What is the influence of photomodification on photosensitized tumour therapy?


Vilnius University
Laser Research Center
Sauletekio al. 9, C. III
2040 Vilnius, Lithuania
Phone: (370 2) 76 94 77
Fax: (370 2) 77 56 23
E-mai: ricardas.rotomskis@ff.vu.lt

Photodynamic therapy referred by us as photosensitized tumour therapy (PTT) has attracted interest as a new technique with the potential for selective local destruction of malignant tumours. It is based on systemic administration of photosensitizers, which may be retained selectively in tumours relatively to the surrounding normal tissue and can be activated by light to produce a local cytotoxic effect (Fig.1).

Efficacy of PTT depends on both the concentration of a sensitizer in cancerous tissue and the illumination dose, since only the excited sensitizer can initiate destruction of malignant cells. The photochemical definition of photochemical dose (PD) is:

Photochemical dose = Concentration of photosensitizer * light dose (1)

Geometrically, the photochemical dose is defined as an area under the curve of sensitizer's concentration plotted as a function of light dose (Fig.2). A more general way in which the geometric definition of PD can be expressed is

where j is a light dose in J cm-3 absorbed at any point of the tissue, and D(j) is a concentration of sensitizer at the same point which varies as a function of j. [ 1]. If sensitizer is stable and no degradation takes place on light illumination the PD can be estimated by a simple multiplication of D and J0.

It is well known that most of sensitizers used in PTT are not stable under illumination with visible light [1-15]. Thus, the influence of photobleaching of sensitizer on the photochemical dose needed for full destruction of tumour should be taken into account [1, 5-8]. If the bleaching follows exponential decay:

where D0 is a concentration of the sensitizer at the beginning of illumination, J0 is the incident light dose, J cm-2, b is a rate constant of the decrease of sensitizer concentration, J-1cm-2, then PD after integration can be expressed:

On the other hand, the photodestruction of most porphyrin-type sensitizers is accompanied by the formation of the photoproducts [9-15], which can be important in PTT.

In this paper we present our studies on the light-induced spectral changes of different sensitizers used in PTT. These changes occurring during PTT could influence sensitization process [16] and should be taken into account in estimation of photochemical doses.