Intratumoral Spatial Distribution of Hypoxia and Angiogenesis Assessed by 18F-FAZA and

The hypoxia-inducible factor-1a (HIF-1a) activates angiogenesis in response to cellular hypoxia, suggesting a spatial correlation between angiogenesis and tissue hypoxia.Methods: Using dig-ital autoradiography of coinjected 18F-labeled azomycin arabino-side (8F-FAZA) (assessing regional hypoxia) and a glycosylated RGD-containing peptide (125I-3-iodo-DTyr4-cyclo(-Arg-Gly-Asp-DTyr-Lys(SAA)-), or 125I-Gluco-RGD) (assessing angiogenesis via binding to avb3 integrin receptors on endothelial cells) performed on 22 EMT6 tumor xenografts, we investigated the intratumoral spatial distribution of these tracers. We applied a Bayesian bivariate image analysis using the mean tumor-to-muscle ratio as a discriminator, resulting in 4 groups: FAZA high/RGD high (Q1), FAZA low/RGD high (Q2), FAZA low/RGD low (Q3), and FAZA high/RGD low (Q4). In an additional 18 xenografts, the immunohistochemically derived HIF-1a protei