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In 1998 a new second-generation photosensitizer was introduced in Russia - a chlorin e 6 derivative named Photodithazine - water-soluble preparation with absorption peak at 668 nm. This novel preparation has passed pre-clinical in vitro and in vivo studies. In 1999 a limited series of clinical testing of photodynamic therapy with photodithazine has been performed in the State Research Center for Laser Medicine of Russian Ministry of Public Health. In comparison to hematoporphyrin derivative (Photofrin, Photosan, Photoheme etc.) and aluminum phthalocyanine (Photosense) used in clinical practice, Photodithazine has a number of special properties. Most significant of them is rapid tissue accumulation and clearance from the organism within 48 - 72 hours. Photodithazine was used as a photosensitizer for treatment of 44 patients with malignant tumors of skin, oral cavity, larynx, bronchi, esophagus, stomach, vulva and other locations. The dose of photodithazine ranged from 0,8 to 1,2 mg/kg of body weight. Laser irradiation has been performed on a solid-state laser device Poljus-2 with wavelength 670 nm and output power 1000 mW. Energy density ranged from 100 to 400 J/cm 2 . Laser irradiation of the inner organ was performed via flexible endoscope. PDT with Photodithazine was not accompanied with systemic and local complications. The treatment was well-tolerated by the patients, including those with severe accompanying diseases, There were no complications associated with possible high skin photosensitivity in all treated group. Therapeutic effect took place in all cases, including complete tumor regression in 22 cases (53,7%) and partial regression in 19 cases (46,3%). By present time clinical PDT with Photodithazine is in the initial state. Photodithazine-based PDT appears to be a very promising technique, but analysis of long-term follow-up results is necessary to confirm its therapeutic efficacy. Further research is required to estimate adequate doses of drug and light for various types of tumors.

In vitro and in vivo biological evaluation of a novel drug substance 'photodithazine' has been performed. In vitro photocytotoxicity (EC50) was 1 (mu) M together with some cytotoxicity. In vivo acute toxicity has been found to be 170 mg/kg for KD10, 175 mg/kg for LD16, 197 mg/kg for LD50, 220 mg/kg for LD84 following 1 percent aqueous solution i.v. injection. Pharmacokinetics and biodistribution studies have been done using the same mice bearing inoculated under the skin of the flanks T36 embryocarcinomas injected i.v. with 40 mg/kg dose of the drug. Maximal tumor and most organs' uptake was attained 1 h.p.i., however, the drug's level in the organs rapidly decreasing to zero with the best tumor/muscle ratios over 10 by 5 h.p.i. 'Photodithazine' has been found to possess rapid clearance from the organism: 94 percent elimination 24 h.p.i. and 98 percent to 48 h.p.i. PDT has been performed in vivo involving 21-23 g A/Snell mice with the same type 0.9-1 g tumors injected 40 mg/kg drug i.p., with 670 nm light being delivered 5-6 h p.i. at different doses. The best irradiation dose has been found to be 170 J/cm2 with a sound necrotic effect and 1-3 week remission. Thus, 'Photodithazine' represents a potent photosensitizer for PDT.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Deuteroporphyrin IX derivatives are prospective PDT porphyrin photosensitizers (PS). The photodynamic effects of 6 new amphiphilic deuteroporphyrin derivatives with different hydrophobicity, as well as effects of known photosensitizers Photoheme and Photosens (used for comparison) on the firing of isolated crayfish mechanoreceptor neuron have been studied. After 30 min photosensitization, neurons were irradiated with He-Ne laser (632.8 nm, 0.3 W/cm2), and changes in neuron firing frequency were recorded. It has been shown that neuron firing is very sensitive to photodynamic impact and can serve as a sensitive indicator of cell photodamage.

The analysis of photoconductivity (PC) spectra in PbTe(Ga) single crystals and films shows that a pronounced photoresponse is observed at an energy approximately 20 meV less the energy gap value. The relative amplitude of the sub-band photoresponse depends on the method of the crystal synthesis, but its energy position does not depend on temperature or growth technique. For PbTe(Ga) thin films the structure of the absorption edge is similar to undoped PbTe and amplitude of the sub-band photoresponse appears to be small. The phenomenological description of the PC kinetics of the investigated samples under the IR-radiation of pulse and heat sources is done. It is established that under the radiation with pulse duration 10 mcs the characteristic relaxation times are 10-3 s at 4.2 K, and the persistent PC can be observed only under the continuous radiation at T < 80 K. Moreover, at low intensities of the continuous radiation PC relaxation time is about 1 ms and only the increase of radiation intensity results in appearance of the persistent PC with the relaxation times of 105 s. We propose a phenomenological model of energy spectrum and impurity states in PbTe(Ga), which is able to describe the experimental data. According to this model the metastable impurity states 20 meV lower the bottom of the conduction band exist in addition to the ground states 70 meV lower the bottom of the conduction band. The increase of the radiation intensity provides the growth of the metastable states concentration and the impurity band formation. So it can be concluded that PbTe(Ga) may be considered as an advanced material for the multispectral photodetectors operating in near IR-region if the ground state electrons are excited and in far IR-region if the excited from preliminary induced metastable states.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The most important features of Pb1-xMnxTe(In) solid solutions are the effect of Fermi level (FL) pinning and the existence of metastable electronic states resulting in the appearance of the relaxation processes of long duration. The increase of MnTe content in Pb1-xMnxTe(In) leads to the shift of pinned FL towards the conduction band edge Ec and metal-dielectric transition at X approximately 0.05. The kinetic processes under the radiation of Pb1-xMnxTe(In) single crystals have been investigated in the temperature range 4.2-35 K. It has been found that under the composition X variation the view of kinetic curves changes qualitatively. At X

Polybiotinylated porphyrinoids and linear alkyl-dibiotins were used to describe accumulation behavior of avidin and POD-labelled avidin on tumor cells preincubated with biotinylated monoclonal antibodies. The accumulation behavior followed more a liner than a formerly postulated branched pattern. This allows for us to calculate necessary repeats of accumulation in order to acquire the necessary amount of sensitizer molecules per tumor cell at low concentration of tumor specific marker molecules at the cell surface.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The accumulation of fluorescent dyes and anticancer drugs in tumors is a fundamental requirement for tumor-diagnosis and therapy. We tested various photosensitizers on vascularized microtumors in the hen's egg test system according to their distribution and accumulation by in-situ videofluorescence microscopy and their influence on tumor blood flow by laser- Doppler spectroscopy. Only 2,4-di((alpha) -methoxyethyl)- hematoporphyrin showed strict tumor localization while diglucosamidyl-heptyl-chlorin labeled cell membranes exclusively. Results from laser-Doppler spectroscopy did not show any influence on tumor blood flow. Intelligent combining of the properties of these sensitizers with accumulation strategies should show in principle strict tumor localization without targeting of non-tumor tissues.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

epu1is', Igor Ponomarev2Laboratory pf PDT, Lithuanian Oncology Center, Vilmus 2600Lebedev Physics Inst. Moscow 117—924ABSTRACTThe correct selection of patients is the most difficult part of the laser treatment. Since 1985 the total number of patientstreated by us using different laser systems was 1544 (2622 benign and malignant skin lesions). High power lasers: Nd:YAG and CO2 lasers were used by us for surgical treatment. Low power lasers: Helium-Neon (gas), Coppervapour, Goldvapour and Dye lasers were applied by us to PDT or to treatment of port wine hemangiomas. This paper reports our effortsin selecting the patients with different skin lesions for the treatment with different laser systems.Key words: Skin lesions, different laser systems.INTRODUCTIONSince 1963 when Leon Goldman pioneered the use of the laser in dermatologic surgical procedures, laser treatment hasgained rapid recognition in the medical centres in USA and Europe. Little specific infoprmation is available on the diffusionand use lasers in Europe.The data presented in Table 1. depicts the number of high power lasers for medical or health care purposes in a numberof selected countries in 19912.Table 1. The number of lasers and lasers per million population in selected countries in 1990—1991Country No of Lasers

The theory is presented for the resonant diffuse scattering in multilayer nanostructures. The dynamic diffraction effects are taken into account. The computational simulation was constructed from this theory and results are presented and discussed. The angular spectra of the diffuse scattering intensity have been measured experimentally. These results confirm the decisive influence of the dynamic diffraction effects on the process of the resonant diffuse scattering.

New advances of copper vapor laser (CVL-laser) have been studied. Two wavelength radiation of the laser (511 nm and 578 nm) gives deeper permeability into organic tissues. Besides, the short pulse prevents the warm relaxation of small vessels. The technical data of CVL-laser: operating regime -- pulse, pulse duration -- 20 ns, pulse frequency 15000 pulse/sec. The shutter works in intervals from 0.05 to 2.0 sec. The power varies in accordance with wavelength: 511 nm (green) -- 1.5 W, 578 nm (yellow) -- 1, 2 W. The diameter of coagulate may be different: 100, 150, 400, 1000 mkm. We chose CVL-laser 'Femta,' created by P. N. Lebedev Physical Institute of RAS, for ophthalmological use. Thirty eight eyes of 37 patients with different types and stages of glaucoma were studied and treated with CVL-laser. The operations of photomydriasis, gonioplasty and trabeculoplasty have been performed. CVL- laser demonstrated efficient application in treatment of interior eye segment of glaucoma patients. The advantages and disadvantages of the CVL-laser application in glaucoma surgery were discussed.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

One of the main problems which arise employing PDT is the patient's sensitization to the sunlight during a 4 - 6 week period after the i/v photosensitizers injection. Applying PDT for patients with head and neck cancer there often is the possibility to inject photosensitizer (the doses of photosensitizer used were many times smaller than in ordinary PDT) intra-arterially (i/a). This is followed by immediate tumor irradiation with laser light. The absorbed light's energy dose is the same as the dose usually used during the PDT. Since 1989 172 head and neck tumors were treated by us applying ordinary PDT and for 17 foci of oral cancer we provided intra-arterial photodynamic therapy. The result of i/a PDT was the same as in usual usage of PDT. But i/a PDT enables the usage of much smaller doses of photosensitizer. Patients need not be protected from the sunlight. I/a PDT enables us also to use effective but quickly splitting photosensitizers.

The photodynamic therapy is highly promising for its dual specificity, namely, for the site of accumulation of the phototoxic substance and for the site of action of laser. A drawback of the PDT technique is a low selectivity of the photosensitizers accumulation in tumor tissue. Therapeutic doses of photosensitizers are fairly high, that leads to unfavorable effects (toxicoses, lesions of normal skin, prolonged rehabilitation). This drawback can be overcome is photoimmunotoxins are used, i.e. conjugates of photosensitizers with antibodies to specific tumor markers. We tried to introduce a simple model for estimation of singlet oxygen effect on cells for the case of free photosensitizers, presented in outside solution, and in case of conjugated dye, bound by cell surface receptors. To achieve the same effect the required concentration of conjugated photosensitizer can be significantly decreased (50 to 100 fold) as compared with free dye. Methods for porphyrins and different phthalocyanines and naphthalocyanines conjugation with protein were developed. The use of bacteriophage T4 as a model for studying the action of photoimmunotoxines on virus, unambiguously demonstrated the applicability of this approach for targeted destruction of viral particles.

The results of laser therapy present in 374 patients with erosive-ulcerous and inflammatory damages of respiratory organs and of gastro-intestinal tract after oncological operations. Two types of laser namely endoscopic laser on the basis of He-Ne and Cu laser were used as sources of radiation. It was shown high therapeutic effectiveness of laser therapy. This method may be recommended for the above-mentioned category of the patients.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Compact sealed-off gold vapor laser (GVL) with 2 W average power and 628 nm wavelength was used for endoscopic photodynamic therapy in 20 patients with different tumors in respiratory system and upper gastrointestinal tract. Russian-made hematoporphyrin derivative (Hpd) `Photohem' was used as a photosensitizer. It was given intravenously at a dose of 2 - 2.5 mg/kg body weight 48 hours prior to tumor illumination with 628 nm light from GVL. Intermittent irradiation with GVL was done through flexible endoscope always under local anaesthesia at a power of 200 - 400 mW/sm2 and a dose of 150 - 400 J/sm2. 80% patients showed complete or partial response depending on stage of tumor. In cases of early gastric cancer all patients had complete remission with repeated negative biopsies. No major complication occurred.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The kinetics of photosensitizer distribution and elimination have been studied using fluorescent methods in organs and tumors of A/Snell mice with embriocarcinoma inoculated into their thigh muscles for the porphyrin compound 2,4-di((alpha) -methoxyethyl)deuteroporphyrin-- IX (DMH, `Dimehin') and its complex with polysaccharide chitosan. DMH fluorescence differs in samples of liver and faeces which follows from the spectra comparison. DMH is metabolizable upon passing through liver into a form eliminated by the gastrointestinal tract as our pharmacokinetic data have shown. DMH has been found to be a short-term highly photodynamically efficient photosensitizer judging by combined analysis of our toxicological, pharmacokinetic and photodynamic research data. DMH-chitosan uptake and distribution studies have shown the complex's long-term persistence in blood circulation, high level accumulation in spleen and lungs, whereas there was no complex registered in tumors and other tissues following i.v. administration.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Vascular effect of PDT has been studied in patients with corneal vascularized leucomas (10 patients) and in patients with corneal neovascularized transplant (3 patients). For vascularized leucomas the method of photodynamic therapy consisted of the local injection of dimegin (deiteroporphyrin derivative) into the space of the newly-formed vessels under operating microscope (opton) with the microneedle (diameter 200 microns) and corneal irradiation by the operating microscope light. For corneal neovascularized transplant the injection of photogem (hematoporphyrin derivative) intravenously were made with subsequent irradiation by light of dye laser (5 hours after the injection) with light density of 150 mW/cm2 for 15 minutes. In all the cases at the time of irradiation the aggregated blood flow was appeared, followed by blood flow stasis. In postoperative period the vessels disintegrated into separate fragments which disappeared completely after 10 - 15 days. Taking into account the data of light microscopy, the disappearance of the vessels took place as a result of the vascular endothelium lisis along the vascular walls. Neovascularized cornea and newly-formed vessels in tumor stroms have much in common. The vessel alterations study presented in this paper, may serve to specify the mechanism of photodynamic destruction of neovascularized stroma of tumor.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

In the problem of the use of lasers for photodynamie therapy (PDT) it will be very interesting to use compact laser without special condition for its exploitation. As previosly reported (1), a using of the gold vapour laser (GVL) is very effective for PDT. We create a GVL with 2 W average power. We use a sealed-off laser tube produced on the base of progressive metal-ceramic technology. A length of the tube is 700 mm. Active length - 400 mm. The diametre of tube is 12 mm. A pressure of neon buffer gas is 200 torn

From 1989 to 1994 more than 600 various malignant foci were treated by more than 400 courses of PDT in the Lithuanian Oncology Center. During the application of PDT we used the following lasers: 35 MW He-Ne laser with 630-1 nm wavelength; 100-300 MW dye lasers with a wavelength of 629-3 nm, and a 100- 300 MW gold vapor laser, with a wavelength of 629-1 nm. We noticed some differences in results between the low-power lasers and the high-energy lasers. The initial response was better in patients whose tumors were irradiated with high-energy lasers, but the was more recidivism in this group. The most interesting thin we noticed was that there were significant differences in response of tumors of various histogenesis. for example, in most cases there was full necrosis of basal cell carcinoma immediately after PDT, but there were only some necrobiotical changes at the same time in other malignant tissues. Full necrosis in squamous cell cancer was noticed ont he third to fourth day after PDT. Full necrosis of malignant melanoma was noticed on the fifth to tenth day after PDT. It is important to emphasize that full melanoma necrosis was more frequently observed in cases where the low-power He-Ne laser was used for the PDT.

A novel type of highly efficient phosphorescent labels is proposed for time-resolved phosphorescent immunoassay (TR-PIA). The phosphorescent properties of palladium and platinum coproporphyrins and different derivatives of tetraphenylporphyrin were studied in deoxygenated micellar solution and at the dry surface in the presence of oxygen. Lifetime, quantum yield, and quantum efficiency in time-resolved mode of phosphorescence measurements for more than 20 compounds were determined. At the optimum condition the detection limit of Pd- or Pt-coproporphyrin of 10-13M may be achieved. The labels are thermodynamically and kinetically stable and insensitive to contamination of solutions and samples with ions of heavy metals. The measurement of room temperature phosphorescence of metalloporphyrin in micellar solution are rather simple and highly reproducible, the phosphorescent signal is stable for several hours and microtiter plates are suitable for micellar and dry surface measurements. Techniques have been developed for covalent and non-covalent labeling of proteins and oligonucletides with the phosphorescent label. The labeling proteins can be stored in the lyophilized state rather long and retain their immunological properties.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

For the first time a method is proposed for targeted destruction of viral particles with a photoimmuno-toxin. The photoinununotoxin is a conjugate of antibodies and dimethoxy haematoporphyrin (a potent singlet oxygen generator), binding with the viral particle and upon illumination with visible light inactivating the virus by singlet oxygen. The method can be used to combat viral infection in humans and to prevent lysis of industrial micro-organisms by lysogenic bacteriophage strains.

In quantitative fluorescence immunological determinations of an antibody or an antigen the measurement is usually provided with an easily detectable marker. A special problem in fluorescence determinations is that serum, microorganisms, and sections have a relatively strong autofluorescence that gives rise to high background levels for most fluorescence markers. A general approach for the elimination of background emission of biological substances is time-resolves measurement with microsecond resolution. For excitation in the UV range, especially for surface measurement, it is necessary to use special optical components with low background phosphorescence, fluorescence, afterglow, and high UV transmittance. Such optical components are not easily available. The requirement of a marker that is suitable for the surface measurement of biological substances are that in addition to the requirement for solution measurement the excitation wavelengths must be in the visible range. In this paper metalloporphyrin phosphorescent markers meeting this requirement are described.

Pd-coproporphyrin I (Pd-CP) has optimum phosphorescence characteristics for application in immunoassay. The aim of this study is to work out a universal phosphorescence immunoassay method (UniPhIA) using monoclonal antibodies to Pd-CP and conjugates of various proteins with Pd-CP for detection of insulin. Pd-CP and monoclonal antibodies obtained allow a convenient method for determination of various antigens to be developed, which combines the universal character of the amplified enzyme-linked immunosorbent assay (a-ELISA) with a high sensitivity and the simplicity of the time-resolved phosphorescence immunoassay.

Monomolecular thin solid films containing water-soluble Pt- and Pd-porphyrins were prepared and transferred onto solid supports. Surface active charged polymer on the basis of alkylated polyethyleneimine was used to improve extraction of the dye from aqueous solution to the interface. The solid-state materials obtained which showed intense long-decay luminescence were studied by optical methods with emphasis to luminescence quenching and lifetime measurements. The results were applied to quenched-luminescence lifetime-based sensing of relative air humidity. A corresponding fiber-optic prototype device was developed.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The x ray emission from femtosecond laser-driven plasma has been investigated using spherical multilayered mirrors. Different laser pulse widths have been used. The conditions required to produce high intensity x ray emission (up to 1011 W cm-2) from H-like excited ions are discussed.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Kinetics of population and depopulation of atomic copper ground state, resonance and metastable levels and also some higher laying levels were measured in active medium of copper vapor laser. A typical commercial sealed-off self-heated discharge tube was studied. Simultaneously at the same conditions of operation characteristics of excitation pulse and gain in active medium were measured. The measurements were made for the whole temperature interval of laser action.