Tissue
hypoxia results from the interaction of cellular respiration, vascular
oxygen carrying capacity, and vessel distribution. We studied the relationship between
tumor vasculature and regions of low pO(2) using quantitative analysis of binding of the
2-nitroimidazole EF5 given to patients intravenously (21 mg/kg) approximately 24 h preceding surgery. We describe new computer algorithms for determining EF5 binding as a function of radial distance from individual blood vessels and converting this value to tissue pO(2). Tissues from six human
brain tumors were assessed. In a
hemangiopericytoma, a WHO Grade 2 and WHO Grade 3 glial
brain tumor, all tissue pO(2) values calculated by EF5 binding were >20 mmHg (described as "physiologically oxygenated"). In these three
tumors, EF5 binding gradients (measured as a function of distance from each observed vessel) were low, with small positive and negative values averaging close to zero. Much lower tissue
oxygen levels were found, including near some vessels, in
glioblastomas. Gradients of EF5 binding away from vessels were larger in
glioblastomas than in the low-grade
tumors, but positive and negative values again averaged to near zero. Based on these preliminary data, we hypothesize a new paradigm for
tumor blood flow in human
brain tumors whereby in-flowing and out-flowing blood patterns may have contrasting effects on average tissue EF5 (and by inference,
oxygen) gradients. Our studies also imply that neither distance to the nearest blood vessel nor distance from each observed blood vessel provide reliable estimates of tissue pO(2).