Polymer Composite for Cancer Therapy
Polymer Composite for Arterial Embolization, Local Hyperthermia, and Interstitial Radiation Therapy in Treatment of Malignant Tumors of the Parenchymatous Organs
Tech Area / Field
- CHE-POL/Polymer Chemistry/Chemistry
3 Approved without Funding
Ministry of Health / Central Research Institute of Roentgenology and Radiology, Russia, St Petersburg
- Russian Academy of Sciences / Institute of Radioengineering and Electronics / Fryazino Branch, Russia, Moscow reg., Fryazino\nI.M.A. Limited Liabilities Company, Russia, St Petersburg
- Huddinge University Hospital, Sweden, Stockholm\nUniversity of Texas / Health Science Center / MD Anderson Cancer Center, USA, TX, Houston\nForschungszentrum Jülich GmbH / Institut fur Schicht- und Grenzflachenforschung, Germany, Jülich
Project summaryAn objective of the offered project is a rise of the treatment efficiency for patients with malignant tumors of parenchymatous organs by the method of complex effect on a tumor with arterial embolization, local hyperthermia and intraarterial radiation therapy.
Cancer is called a disease of the civilization. Frequency of cancer is growing every year. This fact makes scientists search for more effective way of treatment for this disease. Over the last ten years new methods of cancer treatment are found, developed and put into practice, including hyperthermia and intraarterial radiation therapy.
For our applied research we have chosen these very methods of tumor treatment as the most effective and available, not only due to the technique of application but due to the problem that has previously been developed. In the project it is offered to combine the success achieved in certain independent fields such as: embolization, radiation therapy and hyperthermia, into the integrated approach in treatment for cancer of the parenchymatous organs. Prior to the use of this combined method each of them has been improved. This improvement is mainly a guideline of the project activity.
A team of scientists (researchers) who were invited to participate in the project development, has gained great experience in the field of angiographic intervention in embolization of the arterial vessels of the liver and kidney, as well as in treatment for cancer by standard methods of radiation therapy. In order to increase the efficiency of embolization, hyperthermia and radiation therapy, different scientists are drawn into the project, for example, chemists who are the experts in the polymer chemistry and filled-in composites; radiophysicists whose specialization is physics of the magnetic phenomena and ionizing radiation; researchers, whose high scientific potential and great practical experience are used at present in the field of protection of the military engineering from radar detection in the wide frequency range and from intensity of the magnetic fields.
In order to update embolization, it is expected in the project to develop a new embolizing agent, i.e. polymer composite, that might provide a complete , safe and controllable distal/proximal occlusion of the tumor’s blood vessels and might make available to perform interstitial hyperthermia of the tumor.
For this purpose, the polymer composite must have the required rheological properties and contain within itself radio absorbing particles which can absorb the brought electromagnetic power and further transfer this power into the heat at such a dose that will cause a destruction of the tumor.
Value of this thermal dose will depend upon the properties of radio absorbing material, upon a coordination of these properties with characteristics of the given electromagnetic field of the radio frequency range, as well as upon how complete the blood flow is “cut off” in the tumor, since it is the blood flow that is mainly responsible for taking away the heat out of the warmed-up tumor. A maximum thermal dose, achieved within a short time of warming-up (not more than 10 min), that affects selectively the tumor, will harm tumoral cells and will kill them by immune mechanisms. As a rule, hyperthermia is used for treatment of inoperable, recurrent, resistant tumors. It causes a destruction of the tumor and increases its sensitivity to other effects, for example, to radiation therapy.
In order to increase a destructive effect of the hyperthermia, the particles of ionizing radiation can be introduced to the composite, if needed. Radiation therapy, being a local/regional radiation method of treatment for malignant tumors, in our case can give an effect on an improvement of the results of treatment of both primary tumor and area of subclinical tumor spread in the adjacent healthy tissue, lymph tracts, lymph nodes of the first level and sometimes of the second level. Since it is known that not less than one thirds of cancer patients die due to both non-healing of the primary tumor and distant metastases. Advantage of the offered method is that hyperthermia of the tumor can be done immediately after a post-embolization period (this period is accompanied by a fever and inflammatory responses of the embolized organ). Hyperthermia can be done immediately or in some time after a period of half-life of the radiation source. It is noted that the largest damage of DNA is achieved when hyperthermia follows radiation therapy.
This method of complex damage of the tumor as a mini-traumatic palliative treatment for malignant tumors is a new one. It accumulates successful results of embolization, hyperthermia and radiation therapy, which have been used as independent treatment, and it develops them further. This method can be applied only with the use of above mentioned composite. This composite can bring particles of radio absorbing and radio isotope materials into the vessels, but also keep them firmly in the vessels. Thus, success of the method will to a great extend depend upon the completeness of embolization of the tumor vascular system, even distribution, keeping of the radio absorbing and radio isotope particles within the vascular bed, the efficiency of the tumor’s warming-up, dose of ionizing radiation, the proper sequence of thermo- and radiation therapy.
In the course of fulfilment of the project the following results will be received:
- new embolizing agent for distal and proximal embolization of the arteries of the kidney and liver will be developed and implemented into the clinical practice;
- technology will be developed to administrate the radio absorbing and radio isotope particles into tumors’ arterial vessels and to hold them firmly there;
- method’s instructions on the use of the polymer composite for embolization of the arterial vessels will be certified in the Ministry of Public Health of the Russian Federation;
- conditions will be determined to run local radio absorbing hyperthermia of the tumors (effective absorbers of radiomagnetic waves are recommended, as well as characteristics of the electromagnetic field, conditions for “cutting-off” of the regional blood flow, optimal time for running of hyperthermia after embolization, the value of maximum thermal dose, counter-indications for embolization and hyperthermia);
- technique of assessment of the tumor respond to embolization, hyperthermia and radiation therapy will be developed;
- practical recommendations will be developed on selecting of the radio active isotope for this method of treatment;
- technique will be developed for an assessment of the dose field of the ionizing b-radiation in order to run intra-arterial radiation therapy;
- criteria will be developed for an assessment of the efficiency of the thermal-radiation therapy in experiment and in the clinical practice;
- permit of the New Medical Engineering Committee of the Ministry of Public Health of the Russian Federation will be received on application of the polymer composite in medicine;
- industrial production of the polymer composite for arterial embolization will be organized based on a commercial backgrounds;
- installation will be designed for running of hyper-thermo-radiation therapy and it will be prepared for practical use;
- documentations will be drawn out allowing to run medical trials of the hyper-thermo-radiation in the clinical application.
In the offered project 50% of labor costs are made by researchers and specialists who have knowledge in the military field. Due to this fact during three years the mentioned specialists will be engaged in settling peaceful problems dealt with medicine.
Amounts of work include: synthesis and study of the properties of polymer systems and their application for transcatheter embolization, study of transportation and intratumor accumulation of the radio absorbing and radio isotope particles, study of the mechanism of absorbing of electromagnetic power by radio absorbing materials; development of conditions and modes of hyperthermia, its hardware; study of the type and power of the radio isotope radiation, chemical form of the marked composition, value of specific activity and effect of the mentioned factors on destructive changes in the tumor’s tissue.
Main stages of the work on the project include experimental studies, a phase of clinical trials of the method and coordination of the recommendations for trials and treatment at the Ministry of Public Health of the Russian Federation.
Modern methods of vascular and radiation diagnosis will be used for the work, as well as methods and measurements devices for studying of magnetic and dielectric properties of the radio absorbing materials, thermometric methods; rheological and kinetic methods of studying of the properties and processes of hardening of the polymer composite systems, study of the autoradiolysis effect on the physical and chemical characteristics and performances (rheological properties, kinetics of hardening, inertia capacity of the polymer system) and etc.; methods of mathematical simulation for a control of the temperature field in bio-tissues.
Dr. Bo-Goran ERICZON will be the project collaborator who is a director of Liver Transplantation Service at the Huddinge Hospital in Stockholm (Sweden). Dr.ERICZON is engaged in liver transplantation; as a method of treatment for liver pathology. Dr.ERICZON has expressed his interest in a development of the combined treatment method (embolization, hyperthermia and radiation therapy) as an alternative for liver transplantation, since the latter is possible only for a small group of patients. Dr. ERICZON’s role will be to assess the results of the combined method, to express the opponent’s opinion, to take part in joint discussions and to search for the ways of joint participation in symposiums, meetings.
Application of the combined method of effecting the tumor with embolization, hyperthermia and intra-arterial radiation therapy in clinical practice will enable to increase a rate of survival and an average life-time of the patients with III and IV stages of cancer.