Kenneth Krohn

Quantifying Hypoxia with Radiolabeled Fluoromisonidazole: Pre-Clinical and Clinical Studies

The efforts to image hypoxia in oncology were stimulated by several questions about tumor biology and its role in response to treatment. What biochemical or physiological properties of tumors influence outcome of therapy? What drug or molecule is a natural substrate, precursor, or marker for the property of interest? Which characteristics of tumors are quantitatively, if not qualitatively different from normal tissues? Tumor hypoxia emerged as a feature that limits response to both radiation and chemotherapy and distinguishes tumors from nondiseased normal tissues, which are adequately oxygenated. It also appeared amenable to quantitation with PET imaging, provided one could develop an appropriate radiopharmaceutical that gave a positive image of oxygen-deprived tissue. A PET image of the metabolic rate of oxygen using [15O]O2 would produce a less desirable negative image for tissue with reduced oxygenation. Consideration of nonmalignant disease also identified two additional conditions where noninvasive quantification of oxygenation might be useful: myocardial infarct and cerebral ischemia.