RT Journal Article
SR Electronic
T1 Coexpression of Herpesviral Thymidine Kinase Reporter Gene and VEGF Gene for Noninvasive Monitoring of Therapeutic Gene Transfer: An In Vitro Evaluation
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1743
OP 1746
VO 45
IS 10
A1 Martina Anton
A1 Constanze Wittermann
A1 Roland Haubner
A1 Marcus Simoes
A1 Sybille Reder
A1 Bryan Essien
A1 Bettina Wagner
A1 Julia Henke
A1 Wolf Erhardt
A1 Steffi Noll
A1 Neil R. Hackett
A1 Ronald G. Crystal
A1 Markus Schwaiger
A1 Bernd Gansbacher
A1 Frank M. Bengel
YR 2004
UL http://jnm.snmjournals.org/content/45/10/1743.abstract
AB Coexpression of a reporter gene and a therapeutic gene may allow for noninvasive monitoring of cardiac gene therapy. We sought to evaluate the usefulness of an adenoviral vector expressing mutant herpesviral thymidine kinase reporter gene (HSV1-sr39tk) and vascular endothelial growth factor (VEGF) 121 in independent expression cassettes (Ad4tk). Methods: Accumulation of 14C-2′-fluoro-5-methyl-1-β-d-arabinofuranosyluracil (FIAU) and 9-(4-18F-fluoro-3-hydroxymethylbutyl)guanine (FHBG) as reporter probes, and secretion of VEGF into medium, were determined for Ad4tk-infected H9c2 rat cardiac cells in vitro. Results: In vitro tracer uptake increased with increasing vector concentration and over time. It was comparable to cells infected with adenovirus expressing only wild-type HSV1-tk (reporter probe: 14C-FIAU) or mutant HSV1-sr39tk (reporter probe: 18F-FHBG). No significant uptake was observed in cells infected with adenovirus expressing VEGF alone. With increasing vector concentration, Ad4tk-infected cells increasingly released VEGF into medium. VEGF production correlated significantly with cellular reporter probe uptake (r = 0.93; P = 0.0003). Conclusion: The usefulness of a vector coexpressing HSV1-tk and VEGF for noninvasive imaging of expression of a therapeutic transgene has been demonstrated in vitro. This approach may allow for future in vivo monitoring of cardiac angiogenesis gene therapy.