In vivo imaging of S-TRAIL-mediated tumor regression and apoptosis.
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.
Shah
Khalid
K
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. kshah@helix.mgh.harvard.edu
Tung
Ching-Hsuan
CH
Breakefield
Xandra O
XO
Weissleder
Ralph
R
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D005910:Glioma / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D008156:Luciferases / Q000032:analysis; D008163:Luminescent Measurements; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D053221:TNF-Related Apoptosis-Inducing Ligand; D047368:Tumor Burden; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases