Hyperthermia exhibits anti-vascular activity in the s.c. BT4An rat glioma: lack of interaction with the angiogenesis inhibitor batimastat

We investigated the anti-vascular activity of local hyperthermia (44 degrees C, 60 min) in s.c. BT4An rat gliomas, and the influence on tumour growth of hyperthermia and the anti-angiogenic compound batimastat (30 mg/kg i.p.). Heat-induced vascular damage was assessed in small (82 mm3) and large (171 mm3) tumours using confocal microscopy and immunostaining for von Willebrand factor. The influence of hyperthermia on tumour blood flow was measured using the 86RbCl method. The anti-tumour activity of hyperthermia (one or two fractions a week apart) and batimastat (7 or 14 daily injections) and various combination schedules were examined. Hyperthermia disrupted 25-50% of the vasculature in the BT4An tumours, and the vascular damage was most extensive in the central part of the large tumours. The heated tumours exhibited a 40-60% blood flow reduction, which persisted until the last measurement after 24 h. One fraction of hyperthermia caused a significant growth delay of 4 days, compared with the control group (p = 0.01), but no additional tumour response was produced by a second heating session. Batimastat had no influence on tumour growth and the combination of drug and local heating did not enhance the tumour response, compared with heating alone. It was concluded that hyperthermia at 44 degrees C for 60min exhibits anti-vascular activity and inhibits tumour growth in the BT4An tumour model. Batimastat had no effect on tumour growth.