In vivo assay of the radiation sensitivity of hypoxic tumour cells; influence of gamma-rays cyclotron neutrons, misonidazole, hyperthermia and mixed modalities.

Tumour cell death can be evaluated in the living mouse by externally measuring the rate of loss of tumour-bound DNA tracer. By sequentially labelling the tumour-bearing animals with IUdR and IUdR 50 h apart, the average tumour cells at the time of the second injection are labelled by IUdR and the euoxic tumour cells are specifically labelled with IUdR. Tumour treatment at this stage of labelling permits the observation of the reaction of euoxic cells and average tumour cells and finally yields data on hypoxic cells and thus on the oxygen enhancement ratio. This information adds to results from tumour control and growth delay. With this technique effects were analysed of 60-Co γ-rays, cyclotron neutrons ( = 6 MeV), misonidazole (500 mg/kg body wt) and hyperthermia (42°C water-bath), or combinations of these. Misonidazole (15 min before irradiation) altered the oxygen enhancement ratio by a factor of 1·5 for γ-rays and of 1·1 for neutrons; when evaluated from tumour-growth delay and TCD-50 misonidazole gave a dose modifying factor of 1·47 for γ-rays and of 1·2-1·3 for neutrons. Based on percentage tumour regression 100 days after treatment, the enhancement ratio from hyperthermia (after irradiation) was 2·75 for γ-rays (at 10 Gray) and 2·2 for neutrons (at 3·2 Gray). For neutrons combined with misonidazole and hyperthermia the ratio was 2·4. These results demonstrate that effects of neutron irradiation may be modified by electron-affinic substances and/or hyperthermia.