Uptake of radiolabeled 2 '-fluoro-2 '-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase gene - The cellular basis for cardiac gene imaging

Citation
Fm. Bengel et al., Uptake of radiolabeled 2 '-fluoro-2 '-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase gene - The cellular basis for cardiac gene imaging, CIRCULATION, 102(9), 2000, pp. 948-950
Citations number
12
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
102
Issue
9
Year of publication
2000
Pages
948 - 950
Database
ISI
SICI code
0009-7322(20000829)102:9<948:UOR2''>2.0.ZU;2-E
Abstract
Background-Gene therapy is a promising approach for the treatment of cardia c diseases. Coexpression of therapeutic genes with a suitable marker gene w ould allow for the noninvasive imaging of successful gene transfer and expr ession via radiolabeled marker substrates, In the present study, such an ap proach was first applied to cardiac tissue. Methods and Results-The combination of the herpesvirus thymidine kinase rep orter gene (HSV1-tk) and radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-ar abinofuranosyluracil (FIAU) was evaluated. H9c2 rat cardiomyoblasts were in fected in vitro with a replication-defective HSV1-tk-containing adenovirus and a negative control virus. The intracellular uptake of [C-14]FIAU increa sed with increasing multiplicity of infection and with time after infection . Uptake in negative controls remained <15% of positive controls. Additiona lly, vectors were applied intramyocardially in Wister rats. The marker subs trate [I-125]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 c ontrols was low (<10% of positive controls). Conclusions-Using an adenoviral vector, HSV1-tk can be successfully express ed in cardiac cells in vitro and in vivo, yielding high uptake of radiolabe led FIAU. The results suggest that imaging transgene expression in the hear t is feasible and may be used to monitor gene therapy noninvasively.