Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1212-1219 |
| Number of pages | 8 |
| Journal | Journal of Nuclear Medicine |
| Volume | 47 |
| Issue number | 7 |
| State | Published - 1 Jul 2006 |
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Keywords
- Br-FBAU
- Gene therapy
- Molecular imaging
- Nonhuman primates
- PET
Cite this
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Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates. / Sander, William E.; Metzger, Mark E.; Morizono, Kouki; Bonifacino, Aylin; Penzak, Scott R.; Xie, Yi Ming; Chen, Irvin S.Y.; Bacon, Jeffrey; Sestrich, Stephen G.; Szajek, Lawrence P.; Donahue, Robert E.
In: Journal of Nuclear Medicine, Vol. 47, No. 7, 01.07.2006, p. 1212-1219.Research output: Contribution to journal › Article
TY - JOUR
T1 - Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates
AU - Sander, William E.
AU - Metzger, Mark E.
AU - Morizono, Kouki
AU - Bonifacino, Aylin
AU - Penzak, Scott R.
AU - Xie, Yi Ming
AU - Chen, Irvin S.Y.
AU - Bacon, Jeffrey
AU - Sestrich, Stephen G.
AU - Szajek, Lawrence P.
AU - Donahue, Robert E.
PY - 2006/7/1
Y1 - 2006/7/1
N2 - 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.
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.
KW - Br-FBAU
KW - Gene therapy
KW - Molecular imaging
KW - Nonhuman primates
KW - PET
UR - http://www.scopus.com/inward/record.url?scp=33747145289&partnerID=8YFLogxK
M3 - Article
C2 - 16818958
AN - SCOPUS:33747145289
VL - 47
SP - 1212
EP - 1219
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
SN - 0161-5505
IS - 7
ER -