PRACTICE OF PHOTODYNAMIC THERAPY USED IN LITHUANIAN ONCOLOGIC CENTER
L. Bloznelite, Doctor of medicine, the Lithuanian oncologic center, Vilnius:
I. Ponomarev, Doctor of physics, The Lebedev Institute of the Russian Academy of Sciences, Moscow
The concerning certain chemical agents capable of, causing, under light effect, biological reactions in a living organism is not new. Experiments on dyes and light used for degrading the basis of a method of photodynamic therapy (PDT). The main object of all the investigations performed in field is to destroy malignant tissues without detriment to healthy ones.
The process causing such a selective influence has not yet been understood completely. It is widely believed that a dye passes into an excited state as a result of light radiation and conveys its energy to the oxygen being present in an intercellular space thereby to generate atomic oxygen. This process leads to the rapid and irreversible oxidation of subcell components, which disturbs cell metabolism and eventually results in the death of cell.
One the photosensitizers (PS) currently used is a substance (HpD), derivative from hematoporphyrin which, on activation, is converted into DHE - dihematoprophyrinether (a Russian analog - preparation FOTOGEM). Said PS meets the criteria imposed on clinic photosensitizes, because it is not toxic in clinic dosages, is activated by laser radiation penetrating the tissues, and has a selective impact on malignant formations.
As for radiation source, the most suitable for photodynamic therapy is radiation with a wave length within 630 nm - it is strongly absorbed by DHE and easily penetrates the tissue. There are types of high-light lasers usable to generate radiation within this range - 1) a variable dye laser with a pump argon laser (ADL), 2) a dye laser with a pump copper laser and 3) a gold vapour laser (GVL). Rapid progress in the field of diode lasers enables one to create laser plants having an average power of up 3 W for a wave length of 675 nm, albeit the output power of diode systems in a range of 630 nm does not yet exceed 15 mW.
All these devices differ as to output characteristics and the interaction of their radiation of their radiation with tissues. Table 1 shows the characteristics of high-power laser system know on the home market, for the photodynamic therapy of malignant tumors.
The dye laser with an argon pumped laser is in actual fact a system of two lasers. A beam of the argon laser is passed through an array of mirrors and is focused into a dye jet in a crossed resonator with a regulation element to obtain a variable wave length at the exit. The system comprises a sophisticated optical part with 14 adjusted mirrors. Because of low efficiency a typical argon laser needs water cooling and requires energy from a power supply network rated for a power consumption of from 20 to 40 kW. The dye laser also needs water cooling. More, the dye is an organic toxic agent, a factor that present the danger for the user and complicates the operation of the laser.
Also, the laser of the second type uses a dye flowing through a glass curette accommodated in the resonator. The latter is formed by an output mirror and variable element. The laser is cooled with water and requires a frequent change of the dye. As in the case of ADL, the dye is toxic and a solvent is inflammable.
The gold vapour laser is operated according to the principle of warming up the gold particles to fusing temperature and evaporation, as a buffer gas, a laser tube uses an inert gas - neon. The sealed-off active elements on gold vapors, elaborated in the Research & Development Production Association ISTOK, feature service life. GVLs generate radiation at a wave length of 628 nm which is stable and not subject to changes as is the case with the dye lasers. The quality of reflecting mirrors is not critical thereof there possess very high light intensification. Compared to argon lasers, the gold vapour lasers have an efficiency 10 times as high, which makes it possible to utilize air cooling.
For photodynamic therapy to be effective, it is necessary to keep to the following rules:
-
- to use the optimum dose of a photosensitizer (2.5 mg/kg for a majority of hematoporphyrin derivatives):
- - density of laser radiation power at the end of wavebeam guide should not exceed 300 mW/cm2 , otherwise coagulation will occur in place of photodynamic effect; the time of irradiation of tumor is determined by power at the end of the wavebeam guide, the volume of the tumor and by density of energy absorber:
T = 13,1 D2E/P,
wherein:
T - time of illumination [min.]
D - diameter of a tumor (a circumscribed circle) [cm2 ]
E - density of energy absorbed by tumor [J/cm2 ]
P - emissive power at the end of a wavebeam guide [mW]
- to irradiate a tumor 20-80 hours after a photosensitizer has been inserted - in case of untimely irradiation, the risk of damaging the normal tissues increases considerably;
- PDT is most effective when the thickness of tumor does not exceed 1.5 cm. With greater dimensions, a portion of the tumor ought to be evaporated or coagulated, using a surgical laser.
PDT`s major side effect is preservation of patient's photosensitivity in course of several days or even weeks upon administration of DHE. This problem is solved by way of protection from sun rays and special protective clothing.
On examination of photochemical reaction in tumor tissues and also on study of the photosensitizing possibilities of tumor therapy, main attention has so far been paid to the search for more selective photosensitizes and creating effective laser system disregarding tumor histogenesis and, what is more, overlooked were such parameters as the light power of a laser with PDT, duration and periodicity of irradiation. From this point of view, it is interesting to compare the efficiency of the photochemical treatment of tumors of different histogenesis. Such investigations are conducted in the Lithuanian oncologic center where PDT has been applied for nine years now.
Three different laser systems have been put to use:
- A laser system comprising a copper laser and dye laser's radiation was focused into the cuvette of the dye laser consisting of a mixture of rhodamine (30 %) and oxazine 17 (70 %). The given laser system radiated light with a wave length of 628+0.5 nm.
- A gold vapour laser (a wave length of 628 nm). This model AURAN has been elaborated in the Physical Institute of the Russian Academy of Sciences especially for PDT.
- A He-Ne laser LGN-104. With PDT the power of radiation used did not exceed 300 mW. Power density did not exceed 300 mW/cm either. Light power density was from 25 to 50 mW/cm for melanotic sarcoma, up to 500 mW/cm for basal cellular cancer. Most frequently used was a power density of 200 mW/cm.
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