Enhancement of in vivo Radiosensitization by Combination with Pentoxifylline and Nicotinamide / 대한치료방사선과학회지

Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the O2 release from RBC. Nicotinamide (N4) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the the FSaII murine fibrosarcoma by oxygenation the hypoxic cells. We observed a significantly enhanced radiation-induced growth delay of the FSaII tumors by PENTO-NA. Thus the enhancement ration was between 2.5 and 2.8 in growth delay assay. The TCD50 of control tumors was about 57 Gy, but that of PENTO-NA treated tumors was about 32 Gy. The TCD50 was modified by a factor of 1.8. We also observed that PENTO+NA, changes in tumor blood flow and intratumor pO2 were measured using laser Doppler flowmetry and O2 microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+NA. Furthermore, we also found that PENTO+NA significantly increased intratumor pO2 from 8 to 19 mmHg. We concluded that PENTO+NA was far more effective than NA alone or PENTO alone. The increase in the response of tumor in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted.

Improving Oxygenation in the Murine Tumors by a perfluorochemical Emulsion (Fluosl-DA 20%) / 대한치료방사선과학회지

In the present study, a perfluorochemical emulsion (Fluosol-DA 20%) did not alter Do and and Dq values on cell survival curve, indicating that the lack of a direct effect of Fluosol-DA 20% on cellular radiosensitivity in vitro. The effect of Fluosol-DA 20% injection in combination with carbogen breathing was determined on the hupoxic cell fraction in SCK tumors. The hypoxic cell fraction in control SCK tumors was 0.39. This value decreased to 0.05 when the mice were i.v. injected with 12 ml/kg of Fluosol-DA 20% in a carbogen atomosphere. The measured mean and median PO2 values with a microelectorde in the control tumors was 9 mmHg and 4 mmHg, respectively. The treatment of the SCK tumors in the host mice with injected Fluosol-DA 20% in combination with carbogen breathing increased the mean and median PO2 values to 67 mmHg and 62 mmHg, respectively. Using carbogen breathing alone caused a moderate increase of tumor PO2. But Fluosol-DA 20% injection alone caused little change PO2 in the tumor. It was concluded that the combination of Fluosol-DA injection and carbogen breathing is an effective means to improve oxygenation of tumors.