BACKGROUND:  In reporter gene imaging, a transgene is introduced into the cells of interest and the expression of activity of the reporter gene leads to the preferential cellular accumulation of an imaging probe. The engineered cells are thus tagged and their presence in the body can be imaging with a variety of non-invasive techniques. Monitoring the behavior of transplanted cells is important since these cells frequently are rejected by the host's immune system or suffer other complications. Alternatively, these systems can be used to study gene expression in vivo by placing a reporter gene downstream from a promoter or regulatory region of interest. Furthermore, if the tag is a also therapeutic agent, this transgene also becomes a suicide gene, inducing apoptosis of the cell to which it is specifically bound. Several reporter gene systems have been developed, but face problems such as unfavorable biodistributions, immunogenicity, and short retention times.

INNOVATION:  Researchers at UCLA have developed a novel reporter gene imaging system utilizing cell surface bound antibody fragments as reporter genes. After transfection with the antibody reporter gene, the animal under study is injected with small molecules that can bind irreversibly to the antibody and that are labeled with a radionucleotide, fluorescent dye, or MRI contrast agent. Then, the cells of interest can be monitored with non-invasive imaging techniques.

POTENTIAL APPLICATIONS 

• Diagnostic and monitoring tool for stem cell therapy, adoptive immunotherapy, and islet cell transplantation
• Cancer therapeutic

ADVANTAGES

• Pharmacokinetics of the reporter probe can easily be optimized
• The employed labeled small molecule labels show rapid blood clearance and low unspecific binding to normal tissues
• Low potential for immunogenicity
• Antibodies provide extremely high specificity for reporter probes
• Better suited for multiplexed imaging of several genes due to the large number of antibodies that could be used for this purpose

DEVELOPMENT-TO-DATE: Specific and stable in vivo binding has been demonstrated using this novel reporter gene system. Currently, the transfection of additional cells lines is underway as well as the development of a radiotherapy system for oncology applications.

Reference: UCLA Case No. 2008-031