Non-invasive scintigraphic monitoring of gene expression in a HSV-1 thymidine kinase gene therapy model.
In vivo transduction of the herpes simplex virus type-1 thymidine kinase (HSV-1 TK) gene and subsequent administration of antiviral drugs such as ganciclovir has emerged as a promising gene therapy protocol for proliferative disorders. However, the evaluation of HSV-1 TK gene expression in transduced tissue has relied on invasive techniques for detection. We now report that HSV-1 TK expression can be detected non-invasively using scintigraphy. The radioiodinated nucleoside analogue, (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU), becomes metabolically trapped in tumour cells transduced with the HSV-1 TK gene on a retroviral vector. Selective phosphorylation of radiolabelled IVFRU by HSV-1 TK results in elevated radioactivity in HSV-1 TK-expressing cells in vitro and in vivo relative to cells lacking the HSV-1 TK gene. Due to low non-target tissue uptake, unambiguous imaging of HSV-1 TK-expressing tumours in mice is possible with labelled IVFRU. We have monitored the process of tumour regression non-invasively during ganciclovir treatment using labelled IVFRU and scintigraphy.
Morin
K W
KW
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Knaus
E E
EE
Wiebe
L I
LI
D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D002460:Cell Line; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D011877:Radionuclide Imaging; D012513:Sarcoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014018:Tissue Distribution
D000998:Antiviral Agents; D007457:Iodine Radioisotopes; D005467:Floxuridine; C060868:5-(2-iodovinyl)-1-(2'-fluoro-2'-deoxyuridine); D013937:Thymidine Kinase