Noninvasive imaging of cardiac gene expression and its future implications for molecular therapy.

Innovative approaches for cardiovascular molecular therapy are rapidly evolving, and translational efforts from experimental to clinical application are increasing. Gene and cell therapy hold promise for treatment of heart disease, but despite progress, some basic principles are still under development. Open issues are, e.g., related to the optimal method for delivery, to therapeutic efficacy, to time course and magnitude of gene expression, and to the fate of transplanted cells in target and remote areas. The use of reporter genes and labeled reporter probes for noninvasive imaging provides the methodology to address these questions by assessment of location, magnitude, and persistence of transgene expression in the heart and the whole body. Coexpression of a reporter gene allows for indirect imaging of the expression of a therapeutic gene of choice. Furthermore, reporter genes can be transferred to stem cells prior to transplantation for serial monitoring of cell viability using gene product imaging. Additionally, functional effects of therapy on the tissue level can be identified using established imaging approaches to determine blood flow, metabolism, innervation, or cell death. Measures of transgene expression can then be linked to physiologic effects and will refine the understanding of basic therapeutic mechanisms. Noninvasive gene-targeted imaging will thus enhance the determination of therapeutic effects in cardiovascular molecular therapy in the future.