PET as a Tool in Multimodality Imaging of Gene Expression and Therapy

Abstract

Gene therapy holds significant promise in the treatment of many human diseases. Although still in its infancy, it is likely that gene therapy will eventually succeed as a general approach to medical treatment. A key force in the rapid evolution of gene therapy will be the ability to image the location(s), magnitude, and time variation of therapeutic gene expression in animal models as well as in patients. To unravel the complexity and dynamics of molecular and cellular events, it is desirable to image reporter gene expression in individual cells, living animals, and humans with the help of a single construct with multiple reporter genes suitable for various imaging modalities. Positron emission tomography (PET) is likely to play a significant role in multimodality imaging by accelerating animal model development and improving the monitoring of patients in clinical gene therapy trials. In this chapter the fundamentals of gene therapy are reviewed including various viral and non-viral delivery vectors. This is followed by a detailed review of specificity of gene therapy, approaches to cancer gene therapy and safety issues. Details of the Herpes Simplex Virus Type 1 thymidine kinase (HSV1-tk), the Dopamine Type 2 receptor (D2R) and sodium iodide symporter gene as PET reporter genes along with their radiolabeled reporter probes (tracers) are presented. Strategies for coupling a therapeutic gene with a PET reporter gene are also discussed. Finally, examples of recent imaging work in human studies are presented. Potentials for Imaging in Gene Therapy