This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Sadelain, M. Articles by Blasberg, R. G. Search for Related Content Social Bookmarking                         What's this?

Imaging Transgene Expression for Gene Therapy

Department of Human Genetics/Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, Blasberg{at}neuro1.mskcc.org

Ronald G. Blasberg

Department of Neurology, Room C799, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021

Imaging transgene activity is of great interest to the development and implementation of genetically based therapies. Gene transfer in human cells and in humans is performed using either viral or nonviral vectors. Vectors are the vehicles used to transduce cells that are either cultured and destined to be transfused or implanted in patients (ex vivo gene transfer) or cells residing in the body (in vivo gene transfer). To illustrate the principles involved in imaging transgene expression, focus was given to the herpes simplex virus thymidine kinase gene (HSV1-tk) and the HSV1-tk ganciclovir "drug sensitivity" cancer treatment protocol. The imaging paradigm is based on an enzymatic radiotracer assay in which the market substrate, radiolabeled 2'-fluoro-1-β-D-arabinofuranosyl-5-iodo-uracil (FIAU), is selectively phosphorylated by HSV1-thymidine kinase and "trapped" in transduced cells. Information is presented that shows that the images of FIAU-derived radioactivity obtained using quantitative autoradiography, single photon emission computed tomography, and positron emission tomography imaging techniques reflect the level of HSV1-tk gene expression.

Key Words: positron emission tomography • gene therapy • herpes simplex virus • thymidine kinase • 5-iodo-2-fluoro-1-β-D-arabino-furanosyl-uracil • tumor • rat • 124I

Journal of Pharmacy Practice, Vol. 14, No. 5, 376-382 (2001)
DOI: 10.1106/WKLK-N777-76CV-P88N


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?