[The current status of the boron neutron capture therapy of tumors].
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Biomedical subjects
Publications and source records attributed to R A Spryshkova.
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C57BL/6 male mice bearing subcutaneously transplanted melanoma B-16 were used to study the applicability of 5-iodine-2'-deoxyuridine labeled with iodine 125 and 131 radionuclides to assess individual tumor response to radiation. The experiments using intact animals and those locally irradiated in the dose of 10 Gy revealed a correlation between excretion of the above-mentioned radioactive labels from tumor area and tumor growth rate for each mouse (correlation coefficient r = 0.93-0.97). 5-Iodine-2'-deoxyuridine excretion rate measurement can be used in express (24-48 hr) tests of individual tumor response to radiation.
Within the interval of 0.25-168 h after intraperitoneal administration of 125I-iodo-desoxyuridine (IDUR) to mice with inoculated melanoma B-16 or sarcoma-180 the kinetics of a radionuclide label (RL) in both tumors was almost the same; the difference were of quantitative nature only. X-ray radiation resulted in an increase in the radioactivity change rate on the first section of the curves of RL clearance, plotted in semilogarithmic coordinates, in both tumors. Differences in the rates in the study groups of animals irradiated at doses of 2; 10 and 20 Gy and their distinctions from the control group were significant. Proceeding from the modern concept of IDUR metabolism a simple mathematical model has been devised where it is assumed that at the initial moment t = 0.25 h general radioactivity measured in vivo over a tumor, results from radioactivity incorporated in DNA which is constant for each irradiation regimen up to a certain time, and the radioactivity of iodide which is released from the body by the exponential law. A formula has been deduced associating the rate of a decrease in general radioactivity on the first segment of a kinetic curve of RL clearance with the level of the label incorporation in DNA. Thus, the applicability of RL IDUR was shown for establishing the quantitative relations between the proliferative ability of a tumor and an irradiation dose.
A study was made of the kinetics of 125I-iodo-desoxyuridine clearance after x-ray irradiation of experimental tumors sarcoma-180 and melanoma B-16 at doses of 2, 10, 20 and 40 Gy. Change in the level of radioactive label within the time interval of 0.25-48 h was approximated by exponential function (r2-0.92-0.98) or straight lines on a graph in the semilogarithmic scale. Their inclination angles differed significantly for the above doses. Correlations were obtained between the ratio of the rates of change of radioactivity in the irradiated and control tumors within the interval of 0.25-48 h after the administration of 125I-iododesoxyuridine and parameters which characterized growth of the above tumors in various irradiation regimens. The analytical expressions obtained are applicable to quantitative assessment of a tumor response to irradiation.
The kinetics of DNA-synthesizing cells and melanocytes in the peripheral and central zones of transplantable B-16 mouse melanoma was studied by the cytometry and autoradiography methods at varying time after single administration of mercaptoundecahydrododecaborate saturated by 10B, a drug used for neutron capture therapy of malignant tumors. The drug was shown to induce proliferation and differentiation on the 1st day after injection (on the 8th day after transplantation). In the next 2 days proliferation did not change and differentiation was inhibited. The stimulation of proliferation and differentiation was more noticeable on tumor periphery, differentiation inhibition in tumor center.
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Mongrel adult albino female rats with multiform glioblastoma transplanted to the right cerebellar hemisphere were given subcutaneous injections of 8 mg/kg of a serotonin-creatine sulphate solution beginning with the 3rd and to the 28th postoperative days. Rats with a tumor inoculated at the same periods and given injections of a physiological saline solution served as controls. The injection of serotonin leads to a significant increase in the survival of rats by 20% as compared to the survival of rats in the control group, but practically has no effect on the life span of sick animals. Consequently, serotonin either produces an antineoplastic effect in which case the animals do not contract the disease, or it has no effect on the tumor so that the animals die of the developing tumor. Study of the tryptophan content in the neoplasm and the 5-OIAA content in urine provides evidence of a disturbed serotonin synthesis and metabolism in these neoplasms.
As established, following a single introduction of phencarol tagged with tritium in a quinuclidine nucleus perorally to rats on the 13th day of gestation its insignificant amounts gain access to the fetus through the placenta. The maximum concentration of the drug in the maternal blood was recorded 3 hours after its introduction, following 6 hours--in the placenta, with the radioactivity continuing to be constant during the first 6 hours in the embryonal tissues. In 48 hours after introduction the radioactive tag is still demonstrable in the study tissues. It is concluded that the drug is largely retained in the placenta, when introduced on the 13th day of pregnancy; on the 21st day of gestation the barrier functions of the placenta declines. The presence of phencarol and its transformation products in the embryonal tissues is confirmed by the method of thin-layer chromotography.
As evidenced no less than 45 per cent of tritium-labelled antihistaminic drug phencarol (quinuclidine-3-diphenylcarbinol hydrochloride) introduced intragastrically to rats is absorbed. The maximal radioactivity in various organs is reached in 1--3 hours, with high specific radioactivity being recorded in the lungs and liver and low--in the brain. The drug or radioactive products of its tranformation are eliminated largely via the gastrointestinal tract and kidneys.
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Principles of an intertissue distribution of D-alpha(5 methyl-3H)tocopherol were studied depending on ontogenesis of animals. The tissues were divided into three groups via kinetics of the label distribution: tissues responsible for transport and recirculation of the vitamin, tissues-consumers from which the third group was derived--endocrine glands with the maximal rate of the label incorporation within a week. In preadolescent rats the rate of the vitamin consumption was high due to increase in hepato-intestinal recirculation and to optimal conditions of tocopherol intestinal absorption. In ageing rats the rate of the vitamin utilization was decreased as a result of lowering of its absorption in intestine but the vitamin E metabolism was increased in the tissue-consumers considering that the label content was decreased in tissues, the intestinal phase was prolonged two-fold and more as compared with young animals and that excretion of the vitamin metabolites with urine was increased. High level of radioactivity in feces appears to occur because of presence of tocopherol nonabsorbed in intestine.