Uptake of Radiolabeled 2′-Fluoro-2′-Deoxy-5-Iodo-1-β- d -Arabinofuranosyluracil in Cardiac Cells After Adenoviral Transfer of the Herpesvirus Thymidine Kinase Gene

Abstract

Background—Gene therapy is a promising approach for the treatment of cardiac diseases. Coexpression of therapeutic genes with a suitable marker gene would allow for the noninvasive imaging of successful gene transfer and expression via radiolabeled marker substrates. In the present study, such an approach was first applied to cardiac tissue. Methods and Results—The combination of the herpesvirus thymidine kinase reporter gene (HSV1-tk) and radiolabeled 2′-fluoro-2′-deoxy-5-iodo-1-β-d-arabinofuranosyluracil (FIAU) was evaluated. H9c2 rat cardiomyoblasts were infected in vitro with a replication-defective HSV1-tk–containing adenovirus and a negative control virus. The intracellular uptake of [14C]FIAU increased with increasing multiplicity of infection and with time after infection. Uptake in negative controls remained <15% of positive controls. Additionally, vectors were applied intramyocardially in Wistar rats. The marker substrate [125I]FIAU was injected intravenously 3 days later, and animals were kille...