Figure 2: Principle underlying the imaging of HIF-1-active tumor microenvironments, using 123I -IPOS. The PTD enables 123I-IPOS to be delivered to all tissues. In normoxic tissues, oxygen-dependent POS degradation occurs and 123I-IBB loses its binding partner and is cleared. In contrast, in hypoxic tissues, 123I-IPOS escapes degradation and is retained within cells owing to its molecular size. Thus, 123I-IPOS allows for specific imaging of HIF-1-active hypoxic microenvironments.