Noninvasive Molecular Imaging to Detect Transgene Expression of Lentiviral Vector in

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 CD341 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-b-D-arabinofuranosyl)-76Br-5-bromouracil (76Br-FBAU) was used as the substrate for the viral tk enzyme. Upon phos-phorylation, 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 trans-planted tk lentiviral vector–transduced CD341 cells. Elimination of 76Br-FBAU was through renal and hepatic excretion. Conclu-sion: 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. Key Words: 76Br-FBAU; gene therapy; PET; nonhuman pri-mates; molecular imagin