Experimental intra-arterial administration of SR-2508 in the rabbit V2 carcinoma model

The use of the nitroimidazole radiation sensitizers, misonidazole and SR-2508, has been limited by a variety of side-effects, principally peripheral neuropathies. In order to increase the effectiveness of radiosensitization and thereby reduce the administered dose of the sensitizers, intra-arterial delivery of SR-2508 was performed and followed with 10 Gy of 4 MeV photon beam radiotherapy in the rabbit V2 carcinoma tumour model. Comparison was made with rabbits treated with an identical dose of SR-2508 given intravenously prior to photon beam radiotherapy. Control animals were treated with radiation therapy only, intra-arterial SR-2508 only, or had no treatment. Neither the radiation therapy alone nor the SR-2508 alone had any effect on tumour growth. In the intra-arterial group, the tumour growth was slower and the size was significantly smaller than all other groups. The results suggest that the intra-arterial infusion of the radiation sensitizer produces greater response of the tumour than intravenous infusion when each is combined with radiation therapy.