Anti Tumors Laser Methods
Investigation of Nonthermal Destruction of Malignant Tumors by Laser Radiation at Different Wavelengths
Tech Area / Field
- PHY-OPL/Optics and Lasers/Physics
8 Project completed
Senior Project Manager
Evstyukhin K N
NPO Astrophysica, Russia, Moscow
- FIAN Lebedev, Russia, Moscow\nCancer Research Center, Russia, Moscow\nRussian Academy of Sciences / A. N. Bach Institute of Biochemistry, Russia, Moscow\nMoscow State University / International Laser Center, Russia, Moscow
- Heinrich Heine Universität Düsseldorf, Germany, Düsseldorf\nPittsburgh University, USA, PA, Pittsburgh\nLaser und Medizin-Technologie, Germany, Berlin
High intensity of metabolic processes in tumor cells make them mostly sensitive to the action of external factors of different origin including action of light. Laser irradiation of tumor tissues is able to launch a chain of photochemical reactions resulting in tumor destruction. The photochemical destruction of tumors is more advantageous than a thermal destruction because it is both more selective toward tumors and implements low-power laser sources. The exogenous photosensitizes are routinely used for this treatment.
Photosensitizer molecules are predominantly accumulated in tumor cells. Being excited by laser radiation, the photosensitizer molecules transfer excitation energy to oxygen molecules driving them into a highly biochemically-active singlet state (1O2). The mechanism of tumor destruction is usually associated 1O2 formation and activity. In terms of photodynamic therapy (PDT) of tumors, the most interest is acquired by implementation of photosensitizers characterized by intensive light absorption in far-red and infrared. The light scattering at these bands is significantly lower and, hence, the light beam deeper penetrates into the tissue.
Extensive implementation of PDT is restricted by the fact that photosensitizers are accumulated not only in the tumor cells but also in non-tumor cells. This effect causes damage to blood and blood vessels. Studying the opportunities of employing endogeneous photosensitizers - components normally present in cells – is interesting and can help avoiding the above restrictions. A lot of natural photosensitizers can be excited by red and infra-red (IR)light. Those can be flavines, porphyrines, linear tetra-pyrrol compounds, products of lipid peroxidation, and different metabolites. Moreover, not only singlet-singlet but singlet-triplet transitions can be excited if the IR excitation is used. The latter opportunity can be provided by oxygen molecules (3O2) dissolved in tissues that can populate excited singlet state under laser irradiation.
Since tissues are supplied with oxygen mainly through the blood flow, the quantitative measurements of blood flow parameters in tumor vessels and monitoring of the microcirculation status in different tissue layers is of great importance. This project assumes designing a multiwavelength laser Doppler flowmetry apparatus and software for it. This project suggests development of multiwave laser Doppler flowmetry and microscopy that particularly enable studying oxygen transport in the microcirculation sysgem. The method of blood-flow monitoring in tumors, as well as microhemodynamics and trans-capillary exchange methods will be developed using hen-embryo test system with xenotransplanted carcinomas.
Aims of the project
1. Medico-biological aims. To assess the mechanisms of nonthermal laser destruction of tumor cells and tissues by measuring the action spectra of photodestruction in red and IR in the following models and biological systems:
(i) solutions containing photosensitizers, molecular oxygen, and chemical acceptors (scavenges) of singlet oxygen (aromatic hydrocarbons and heterocyclic compounds);
(ii) ovary tumor cell cultures (CaOV line, that is routinely used in the Russian Oncology Center for screening antitumor drugs);
(iii) hen-egg test system with xenotransplanted lung carcinoma (OAT 75);
(iv) solid tumors in experimental animals (mice).
The action spectra is to be measured in solutions by the rate of 1O2–acceptor photodestruction; in biological systems – according to average rate of tumor growth, their lifetime, and intensity of transcapillary exchange; in experimental animals – by intensity of transcapillary exchange and using histological survey. The methods of spectroscopic registration of singlet oxygen in models and biological objects will be improvement.
2. Technical aims:
(a) Creation of lasers and means of laser-irradiation delivery for measuring the action spectra of laser irradiation in red and IR wavelength bands, namely, development of an Nd-YAG-pumped (1064 nm) forsterite laser that provides quasi-cw emission of required power level tunable between 1200-1300 nm.
(b) Creation of apparatus for multi-wave laser-Doppler flowmetry and microscopy. Testing methods of (i) microdynamics monitoring, (ii) transcapillary-exchange monitoring, and (iii) oxygen-supply monitoring in tumor tissue.
The ISTC aims. The leading scientists of Scientific-Production Organization “SPA Astrophysics”, who have been previously involved in weaponry development, will be engaged in biomedical research, aimed at improvement of the methods of malignant-tumor treatment. The “SPA Astrophysics” will be ready for producing laser devices for cancer treatment after successful project realization. This will provide job opportunities in SPA construction bureau and create new working places.
New information on the mechanisms of laser destruction of tumors will be obtained in a result of the proposed project. Information about the laser-irradiation action spectra will remarkably develop the method of laser therapy of tumors and will create new laser therapeutic devices and equipment for controlling the necessary irradiation dose.
Technical approach and methodology includes investigation of both the action spectra of laser irradiation and the death kinetics in laser-irradiated tumor cells. This task requires development of laser apparatuses and light-delivery systems as well as development of methods, apparatuses, and software for monitoring hemodynamics and transcapillary exchange by analyzing Doppler spectra of multiwavelength laser light.
Potential role of foreign collaborators
Foreign collaborators will take part in meetings and discussions on the results of the investigations that would be performed in the frames of this project. They will be involved in experience exchange, coordination and correction of plans of studies. Joint test and control experiments are also been planned.
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