RT Journal Article
SR Electronic
T1 Noninvasive Molecular Imaging to Detect Transgene Expression of Lentiviral Vector in Nonhuman Primates
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1212
OP 1219
VO 47
IS 7
A1 William E. Sander
A1 Mark E. Metzger
A1 Kouki Morizono
A1 Aylin Bonifacino
A1 Scott R. Penzak
A1 Yi-Ming Xie
A1 Irvin S.Y. Chen
A1 Jeffrey Bacon
A1 Stephen G. Sestrich
A1 Lawrence P. Szajek
A1 Robert E. Donahue
YR 2006
UL http://jnm.snmjournals.org/content/47/7/1212.abstract
AB Noninvasive imaging of a reporter gene is a new and promising technique to quantify transgene expression after gene therapy. This study was performed to demonstrate visualization of lentiviral-marked cells by PET. Methods: We transduced nonhuman primate CD34+ hematopoietic cells with a lentiviral vector expressing a PET reporter gene, the mutant viral herpes simplex virus type 1–thymidine kinase (HSV1-sr39tk) gene. 1-(2-Fluoro-2-deoxy-β-d-arabinofuranosyl)-76Br-5-bromouracil (76Br-FBAU) was used as the substrate for the viral tk enzyme. Upon phosphorylation, 76Br-FBAU was retained by cells and imaged by PET. The long half-life of 76Br, 16.2 h, permitted us to perform extended pharmacokinetic and imaging studies. Results: 76Br-FBAU was retained in vascular tissues of the animals with transplanted tk lentiviral vector–transduced CD34+ cells. Elimination of 76Br-FBAU was through renal and hepatic excretion. Conclusion: Noninvasive molecular imaging using PET will help us, in the future, to define the contribution and distribution of cells and their progeny to tissue repair and development.