IMPROVED TUMOR OXYGENATION AND RADIOSENSITIZATION BY COMBINATION WITHNICOTINAMIDE AND PENTOXIFYLLINE

We hypothesized that the combination of pentoxifylline (PTX) and nicot inamide (NA) can reduce the radioresistance of FSaII murine fibrosarco ma by improving oxygenation of the hypoxic tumour cells. The purpose o f this study was to test the hypothesis; first, tumour blood flow afte r treatment with NA, PTX, and the combination (PTX+NA) was measured us ing laser Doppler flowmetry. Second, intratumour PO2 after various tre atments was measured polarographically using 02 microelectrodes. Third , the radiation response was also measured, i.e. after an exposure to 20 Gy, the time required to reach a four-fold increase in initial tumo ur volume was 18 days in the saline-treated control group, 21 days in the NA-treated group, 26 days in the PTX-treated group, but was 36 day s in PTX+NA treated group. Interestingly, tumour blood flow significan tly increased at 10 min after injection of PTX+NA. The mean PO2 in unt reated control tumours was 7.5 mmHg, increasing to 13-1 mmHg after 500 mg/kg of NA alone. Repeated injections of PTX with 100 mg/kg/day for 3 days significantly increased intratumour PO2 to 17.2 mmHg. Compared with PTX alone, PTX+NA slightly increased intratumour PO2 from 17.2 to 18.5 mmHg. However, the percentage of regions having values < 2.5 mmH g significantly decreased from 5 % with PTX alone to 1 % with PTX+NA. In conclusion, single or multiple injections of PTX may increase avail able 02 in the tumour and thus ameliorate hypoxia in tumour microregio ns. As previously reported, the subsequent injection of NA may efficie ntly oxygenate acutely hypoxic cells. Consequently, PTX+NA may increas e the radioresponse of tumours by oxygenating chronic as well as acute ly hypoxic cells. PTX alone or in combination with NA is potentially u seful to radiosensitize tumours.