Search

Boron neutron capture therapy (BNCT) may improve the locoregional control of radio/chemoresistant tumours like soft tissues sarcomas (STS). This technique uses the 10B(n,alpha)7Li nuclear reaction to destroy tumour cells, provided that a sufficient amount of 10B may be carried selectively into them. In order to evaluate the targeting potential of 10B-L-borophenylalanine (BPA) a 10B biodistribution study was carried out in 24 Wistar rats bearing Yoshida sarcoma. Six animals received increasing intraperitoneal doses of BPA (300, 600 and 1200 mg kg-1), while the remainder received a BPA dose of 600 mg kg-1 but with a sacrifice at six different time points: 1, 2, 4, 6, 9 and 12 h. The 10B concentrations in the tumours, normal tissues and blood were analysed with neutron capture radiography (NCR). The analysis shows that 36 micrograms g-1 (+/- 4 SD) of 10B may be incorporated into the tumour, with a ratio of 13 (+/- 4 SD) versus the muscle and a ratio of 15 (+/- 3 SD) versus the blood, 6 h after an intraperitoneal injection of 600 mg kg-1 of BPA. The BPA appears to be abundantly incorporated in the tumour, and the kidney proximal tubule area. These data suggest that BNCT using BPA may provide an improved therapeutic ratio for the treatment of STS.

Purpose: Tumor regression is one of the most important factors determinating the tumor control probability after radiotherapy. The changes in the regression of tumors during fractionated radiotherapy and the application of different radioprotectors or radiosensitizers make render to assess their effectivity., Material and Method: The effect of hypoxic breathing (8.1% O2) on the tumor regression of Yoshida sarcoma was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy., Results: No significant changes in the tumor regression after radiotherapy in any group in any time independent from respiratoric hypoxia were recorded. The tumor regression rate was significantly influenced by treatment schedule (p < 0.0005)., Conclusions: Our results support the hypothesis of hypoxy-radiotherapy: The acute hypoxic hypoxia, caused due the breathing of hypoxic gas mixture with 8 to 10% oxygen, did not influence the radiation induced tumor regression in animal experiment. For this criterium no protection can be shown. The influence of hypoxy-radiotherapy on the local tumor control is necessary to evaluate in further experiments.

Purpose: Tumor reoxygenation is one of the most important factors determining the tumor control probability after radiotherapy. In experimental studies reoxygenation has been measured preferably after single dose irradiation. Only few data exist about changes in the hypoxic tumor fraction during fractionated radiotherapy., Material and Methods: The changes in the pO2 during fractionated radiotherapy were studied in Yoshida sarcoma transplanted to Wistar rats. Tissue oxygenation was assessed using a polarographic electrode system at the beginning, in the middle and at the end of radiation therapy. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy., Results: In the statistical analysis significant changes emerged in the mean, median, 10%-percentile and 0 to 2.5 mm Hg and 0 to 5.0 mm Hg values dependent on time. The tumors were significantly more hypoxic at the end of therapy. This trend became more pronounced with decreasing dose per fraction., Conclusions: The Yoshida sarcoma has no effective reoxygenation during fractionated radiotherapy.

Purpose: Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while breathing hypoxic gas mixture during irradiation., Material and Methods: The effect of breathing hypoxic gas mixture (8.1% O2) on pO2 in Yoshida sarcoma and muscle was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. Tissue oxygenation was assessed with a polarographic electrode system., Results: The median pO2 in Yoshida sarcoma was 10 mm Hg. 21% of pO2-values were lower than 5 mm Hg. During breathing of hypoxic gas mixture no significant changes in median tumor pO2 or radiobiologic hypoxic values (< or = 5 mm Hg) were recorded. The median pO2 in muscle was 30 mm Hg. During breathing of gas hypoxic mixture a significant decrease of the median to the value 12 mm Hg and an increase of the radiobiologic hypoxic values (p < 0.00001) were observed. The changes of pO2-values were constant independent from fractionation., Conclusions: Between tumor and healthy tissue exists a significant difference regarding changes in the radiobiologic fraction during breathing of hypoxic gas mixture. This fact explains the experimental and clinical experience, that the breathing hypoxic gas mixture protects the healthy tissue without changes in the radiosensibility of chronic hypoxic tumor tissue.

Yoshida sarcoma cells, which have the same growth characteristics as ascites cells in the mouse and in cell suspension, were partially synchronized in vitro by means of excess thymidine (0.1 mM thymidine for 18 h). The growth of non-synchronized cultures was inhibited by irradiation, the degree depending on the dose of radiation. At the same time, a 50% inhibition in vivo (380 rad) and in vitro (480 rad) was determined. The incorporation of 3H-thymidine into the DNA is inhibited by 10-32%, depending on the radiation dose. The mitotic index decreases 2 h after irradiation by a dose-dependent amount. A mitotic maximum develops later; the delay is dose-dependent. Partially synchronized cells were irradiated in the G1/S-, G2-, and G1-phase. As compared to the 3H-thymidine incorporation and the mitotic index there were no significant differences between the cultures which were irradiated in the individual phases of the non-synchronized control cultures. The cultures which were irradiated in the G2-phase, however, showed a significantly reduced growth in vivo after 48 h. If the cells were cultured for more than 72 h after irradiation, the differences between the cultures irradiated in the G2-phase and the other phases were reduced.