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(Circulation. 2000;102:948.)
© 2000 American Heart Association, Inc.

Brief Rapid Communications

Uptake of Radiolabeled 2'-Fluoro-2'-Deoxy-5-Iodo-1-ß-D-Arabinofuranosyluracil in Cardiac Cells After Adenoviral Transfer of the Herpesvirus Thymidine Kinase Gene

The Cellular Basis for Cardiac Gene Imaging

Frank M. Bengel, MD; Martina Anton, PhD; Norbert Avril, MD; Thomas Brill, MD, DVM; Ngoc Nguyen, BSc; Roland Haubner, PhD; Elisabeth Gleiter, PhD; Bernd Gansbacher, MD; Markus Schwaiger, MD

From the Nuklearmedizinische Klinik und Poliklinik (F.M.B., N.A., N.N., R.H., E.G., M.S.), and the Institut für Experimentelle Onkologie und Therapieforschung (M.A., T.B., B.G.), Technische Universität München, Munich, Germany.

Correspondence to Frank M. Bengel, MD, Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Ismaninger Str 22, 81675 München, Germany. E-mail frank.bengel{at}lrz.tu-muenchen.de

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-ß-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 killed after 24 hours. Autoradiographically, regional transgene expression was clearly identified in animals receiving the adenovirus containing HSV1-tk (3.4±2.2-fold increase of radioactivity at vector administration site compared with remote myocardium), whereas nonspecific uptake in negative controls was low (<10% of positive controls).

Conclusions—Using an adenoviral vector, HSV1-tk can be successfully expressed in cardiac cells in vitro and in vivo, yielding high uptake of radiolabeled FIAU. The results suggest that imaging transgene expression in the heart is feasible and may be used to monitor gene therapy noninvasively.

Key Words: gene therapy • imaging • genes, reporter • arabinofuranosyluracil • radioisotopes

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