The optimum time for irradiation relative to tumour concentration of hypoxic cell sensitizers

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Abstract
It is common practice in the clinical use of the hypoxic-cell radiosensitizer misonidazole to irradiate approximately four hours after oral administration of the drug. This time appears to coincide roughly with peak plasma and tumour levels of misonidazole in patients following oral administration (Wiltshire et al., 1978; Dawes et al., 1978; Urtasun et al., 1977). It has thus become axiomatic that the irradiation should be delivered at the time of peak concentration of drug in the tumour. This principle may also be used in some laboratories in testing new hypoxic-cell radiosensitizers, for which it is often easier to measure tumour concentration and then to test the new sensitizer at the time at which the tumour concentration is at its maximum. The purpose of this report is to show that this assumption can be incorrect: that for some drugs peak tumour levels occur before the time of maximum radiosensitivity of the tumour. This has implications both for the testing of new sensitizers in animal tumours, and...