Comparative effects of combretastatin A-4 disodium phosphate and 5,6-dimethylxanthenone-4-acetic acid on blood perfusion in a murine tumour and normal tissues

Purpose: To compare the ability of combretastatin A-4 disodium phosphate (C A4DP) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) to change tissue blo od perfusion. Materials and methods: The tissues were a C3H mouse mammary carcinoma and v arious murine normal tissues, with perfusion measured using the (RbCl)-Rb-8 6 extraction technique. Results: CA4DP (250 mg/kg; i.p.) reduced tumour perfusion to 34% of that se en in controls within 1 h of injection. It was maintained at this for at le ast 6 h, returning to control levels by 24 h. This decrease was dose-depend ent. DMXAA (25 mg/kg; i.p.) caused a 79% reduction in tumour perfusion 6 h after injection; no recovery was observed even after 24 h. DMXAA showed no changes at doses below 10 mg/kg. Both CA4DP and DMXAA increased perfusion i n the gut, kidney, bladder and lung, while decreasing splenic perfusion. CA 4DP tended to decrease perfusion in muscle, while DMXAA increased liver per fusion. These changes in normal tissue perfusion were generally less than t hose changes seen in tumours. No significant changes were seen in skin. Conclusions: CA4DP and DMXAA produced a selective and significant reduction in tumour perfusion, but the pattern of change was different. These result s suggest how these vascular targeting drugs should be combined with more c onventional therapies.