| Autor: |
Martina, Anton, Constanze, Wittermann, Roland, Haubner, Marcus, Simoes, Sybille, Reder, Bryan, Essien, Bettina, Wagner, Julia, Henke, Wolf, Erhardt, Steffi, Noll, Neil R, Hackett, Ronald G, Crystal, Markus, Schwaiger, Bernd, Gansbacher, Frank M, Bengel |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 45(10) |
| ISSN: |
0161-5505 |
| Popis: |
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).Accumulation of 14C-2'-fluoro-5-methyl-1-beta-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.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).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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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