This triple reporter vector was invented by Gelovani and optimized for stem cells by senior research scientist Brian Rabinovich, Ph.D., and instructor Amer Najjar, Ph.D., of Experimental Diagnostic Imaging. The tri-fusion reporter gene delivers green fluorescence protein for imaging in tissue or cell culture, firefly luciferase for bioluminescent imaging, and the HSV1-tk gene, which is a reporter gene for positron emission tomography (PET) imaging. All three are expressed by the CD34+ cells and their progeny in the mouse hearts and provide the means for long-term monitoring of their fate by repetitive, multi-modal, non-invasive imaging.
Researchers used bioluminescence imaging to study how long the injected stem cells survived in the heart. PET/CT imaging coupled with magnetic resonance imaging (MRI), pinpointed the precise location of stem cells' in the heart muscle.
MRI also was used to measure ejection fraction and to assess the efficacy of the stem cell therapeutic approach for improving cardiac contractile function. This MRI technique relies on an innovative approach developed by co-author Jim Bankson, Ph.D., assistant professor in MD Anderson's Department of Imaging Physics, to match the MRI images to the motion caused by the beating heart, while associate professor Luc Bidaut, Ph.D., had optimized methods to overlay the PET/CT and MR images.
Bioluminescence imaging works well in small animals because the distance between detectors and the photon-emitting cells is short, it is unlikely to work in larger animals or humans for a variety of reasons. The PET/CT and MRI techniques used in the experiment are readily translatable into the clinic, Gelovani noted. The team used a new PET imaging agent called [18F]FEAU which, when acted upon by the HSV1-tk reporter gene, entrapped this radio-labeled PET agent inside the transplanted cells, enabling their detection in the heart by PET/CT imaging.
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center