Synthesis and Characterization of Congeners of Misonidazole for Imaging Hypoxia

whose biodistribution would reflect intracellular oxygen concentration. Specifically, we seek tracers that will localize within cells in inverse proportion to their oxy gen content so that hypoxia can be imaged with positron emission tomography (PET) or single photon emission computed tomography (SPECT) as an intense concen tration of radioactivity. Such tracers may provide a better defined image than possible with 0@@0 and meas urements of rMRO2, the regional metabolic rate for 02. This proposed tracer should initially distribute non selectively throughout all tissues, reaching an early equi librium distribution that is proportional to its partition coefficient in each tissue. An intracellular reaction would then occur at a rate inversely proportional to the intracellular oxygen concentration, to retain the tracer in tissues. Any tracer that was not trapped by this reaction would wash out, resulting in the desired posi tive image of hypoxic tissues. The nitroimidazole radi osensitizers, typified by misonidazole, exhibit these characteristics. Misonidazole exhibits three properties in hypoxic cells: sensitization to ionizing radiation,