A COMPARISON OF THE PHYSIOLOGICAL-EFFECTS OF RSU1069 AND RB6145 IN THE SCCVII MURINE TUMOR

The physiological and therapeutic effects of the bioreductive agent RS U1069 (80 mg/kg i.p.) and its prodrug RB6145 (240 mg/kg i.p.) were inv estigated in the SCCVII tumour. Using laser Doppler flowmetry it was f ound that RSU1069 produced a significant 30% reduction in tumour blood flow 30 min after administration, while RB6145 had no effect. Tumour oxygenation, measured with an Eppendorf oxygen electrode, was unchange d by either agent except for a reduction in values less than 2.5 mmHg at 30 min after injection. Neither agent significantly altered tumour energy metabolism, assessed by P-31 magnetic resonance spectroscopy. B oth agents significantly increased tumour glucose content by a factor of 1.6-1.7 at 30 min after injection, but had no effect on glucose-6-p hosphate or lactate levels, Tumour growth was significantly delayed by heating (42.5 degrees C, 60 min), and although neither RSU1069 nor RB 6145 alone had any effect on tumour growth they produced a similar enh ancement of the tumour response to heat. The therapeutic effects are c onsistent with the known conversion in vivo of one third of the pro-dr ug RB6145 to its active product RSU1069, however the physiological eff ects of the two agents in the SCCVII tumour are not identical.