Effect of local irradiation on tumor oxygenation, perfused vessel density, and development of hypoxia.

Abstract

Based on both direct and indirect studies, tumor oxygenation has been shown to play an important role in clinical radiotherapeutic response. With this in mind, numerous strategies have been devised to minimize or eliminate regions of tumor hypoxia, or low oxygenation. These have included both methods for increasing oxygen delivery to the tumor7 and techniques for directly targeting the hypoxic cells using radiosensitizers or hypoxic cell cytotoxic agents.1 When combining such agents with radiotherapy, it is important to appreciate the effects of the irradiation itself on both tumor blood flow and oxygen distribution. The current study presents a method for combining several sophisticated techniques to obtain a comprehensive two-dimensional mapping of the relationships among tumor vascular configuration, oxygen transport, and hypoxic development following local tumor irradiation. First, tumor oxygen availability is spatially defined by measuring intravascular blood oxygen saturations (HbO2) cryospectrophotometrically in a frozen tumor block. Second, hypoxia development, in relation to the intravascular oxygen availability, is quantified in adjacent histological sections, using immunohistochemical detection of a nitroheterocyclic hypoxia marker (EF5). Third, a combination of fluorescent (DiOC7(3)) and immunohistological (PECAM-1/CD31) stains is used to define the distribution of distances between the tumor cells and the nearest anatomical or perfused blood vessel.KeywordsTumor SurfaceTumor Blood FlowTumor FreezingIrradiate TumorTumor OxygenationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.