SPECTRAL PROPERTIES OF THE PHTHALOCYANINES AND THEIR PHOTOTOXICITY

Hana Kolarova, Roman Kubínek, Miroslav Strnad

Centre of Molecular Biology and Medicine, Palacký University Olomouc,

Department of Biophysics, Faculty of Medicine, Palacký University, Olomouc, Czech Republic

E-mail: KOL@risc.upol.cz, KUBIN@risc.upol.cz

Introduction

In photodynamic therapy (PDT), a sensitizer, light, and oxygen are used to cause photochemically induced cell´s death. The mechanism of phototoxicity involves generation of singlet oxygen and other free radicals when the lightexcited senzitizer loses or accepts an electron.

Efficiency of PDT is affected by factors included:

absorption spectrum of the photosensitizer

wavelenght of the activation light

depth of the light penetration in the tissue

biological tissue answer on singlet oxygen

There are four properties that would make a sensitizer optimal for PDT.

selective retention in tumorous tissue

fast removing from healthy tissue, first of all from skin and eyes

possibility of the activation by longer and depthly penetrating wavelenght

featureless toxicity

Types of photosensibilisers

Phthalocyanines, chlorines and 5-aminolevulinic acid present a new generation of substances for photodynamic treatment of tumors.

Protoporphyrin IX production after systemic 5-aminolevulinic acid administration is very tissue specific.

Phthalocyanines can be chelated with a variety of metals, chiefly aluminium and zinc, and these diamagnetic metals enhance the phototoxicity. Less sulfonated compounds, which are more lipophilic, exhibit the best membrane-penetrating properties and are the most active.

To find optimal therapeutic doses for i. v. or local application, it was necessary to test:

the maximum non-toxic concentration

minimum phototoxic level relate to laser irradiation in different model systems.

Standard testing system for definition of the in vitro cytotoxicity and phototoxicity:

splenocytes obtained from rabbit spleen fragments

B16 pigmented melanoma