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J Korean Soc Ther Radiol > Volume 9(1); 1991 > Article
Journal of the Korean Society for Therapeutic Radiology 1991;9(1): 7-16.
Enhancement of in vivo Radiosensitization by Combination with Pentoxifylline and Nicotinamide
Intae Lee, Moon June Cho
1Department of Therapeutic Radiology-Radiation Oncology University of Minnesota Medical School, U.S.A.
2Harvad Street at East River Road, Box 494 UMHC, Minneapolis, MN 55455, U.S.A.
3Department of Therapeutic Radiology, College of Medicine, Chungnam National University, Dae-Jeon, Korea.
4Cancer Research Institute, Chungnam National University, Dae-Jeon, Korea.
ABSTRACT
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.
Key Words: Radiosensitization, Tumor oxygenation, Pentoxifylline, Nicotinamide, Intratumor pO2, Laser Doppler flowmetry, RBC flux
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