Figure 2.

Theranostic imaging of PI3-kinase with a self-activating viridin (SAV). (A) The SAV consists of wortmannin modified at the C11 and C20 positions. The modification at position C11 resulted in the addition of the fluorochrome, NBD, while position C20 (red arrow) is modified to allow self-activation and conjugation to a dextran chain. When the leaving group (R) at C20 is CH₃, the self-activating construct (SAV) is formed. When R=H the construct is non-activating (NAV). (B) Uptake of injected SAV into the vascularized portions of an implanted xenograft tumor in a mouse ²⁵. Immunohistochemistry of NBD reveals that the accumulation of wortmannin correlates strongly with CD31 expression. (C) Mice injected with the SAV construct (blue line) showed a complete arrest in tumor growth, which was not seen with NAV or dextran. (D) Intravital microscopy of the Cy5.5 moiety revealed that the kinetics of SAV were dominated by the 70 kDa dextran chain. 4 minutes after injection the probe was exclusively intravascular, but by 24 hours it has accumulated robustly in the interstitial space. (white arrow = blood vessel) ²⁵. (E) Anti-inflammatory effects of SAV in a mouse asthma model ¹⁵. Whole-body fluorescence tomography images of the thoracic region show differential protease activity in the lungs. Mice injected with SAV show a marked reduction in protease activity in the lungs. Reproduced with permission.