A new technique for imaging molecular oxygen concentrations in living tissues has been developed. It exploits the sensitivity of the electron spin resonance (ESR) spectra of certain injectable compounds, nitroxide spin labels or spin probes, to molecular oxygen concentration. It is a magnetic resonance technique which thereby provides a noninvasive means of measuring and imaging molecular oxygen concentration in a living animal. Development for human application should be possible. The proposal describes the development of an unusually low frequency (1f) ESR imaging spectrometer for animal (murine) oxygen measureffients and images. The I development of an oxygen sensitive spin probe particularly well sulted for in vivo measurement is described. Its properties are detailed and its ability to prov de oxygen ccncentration measurements froin a live mouse is demonstrated. An image from a phantom consisting of separate water compartments equilibrated with different oxygen partial pressures is presented. Optimization of the oxygen imaging performance of the IF-ESR imaging spectrometer is necessary; a strategy is presented as the initial work. The imaging oxymeter will be applied to problems related to clinical oncology to be studied in experimental murine tumor models. In particular, the role of molecular oxygen in the potentiation of radiation and chemotherapy will be explored. I Experiments will be undertaken with the imaging oxymeter to determine the extent of artificial oxygen concentration manipulations and correlate that extent with therapeutic effect. Images of tumor oxygen concentration will be correlated with outcome of treatment with radiation and chemotherapy. Measurements of the time course of tumor oxygen concentration will be made and used to determine individual mouse radiation dose scheduling. This will be compared with a more rigid and standard schedule. Thus a new oxygen concentration sensitive image will be optimized and applied to the long standing questions concerning the role of oxygen in cancer therapy. It promises to provide answers to questions unanswered after decades of research.
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