In vivo imaging of S-TRAIL-mediated tumor regression and apoptosis

Mol Ther. 2005 Jun;11(6):926-31. doi: 10.1016/j.ymthe.2005.01.017.


Therapeutic proteins with specific effector functions play an increasingly important role in drug therapy. For example, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) predominantly kills cancer cells, while sparing normal cells. Here, we report the use of a secreted version of TRAIL as a therapeutic protein that induces apoptosis and kills surrounding cells in vivo, thus resulting in the dramatic reduction of glioma burden in mouse tumor models. Using a caspase-3-activatable aminoluciferin, we were able to show the induction of apoptosis specifically in S-TRAIL vector-infected gliomas. We also show that S-TRAIL-mediated apoptosis and resulting changes in tumor burden can be imaged in the same animal by dual-substrate bioluminescence imaging. The use of S-TRAIL as a therapeutic protein and the ability to image noninvasively both apoptosis and any other cellular events in real time have important clinical implications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Caspase 3
  • Caspases / metabolism
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Glioma / pathology*
  • Glioma / therapy*
  • Humans
  • Luciferases / analysis
  • Luminescent Measurements*
  • Membrane Glycoproteins / genetics*
  • Mice
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Burden
  • Tumor Necrosis Factor-alpha / genetics*


  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Luciferases
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases