Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates

William E. Sander, Mark E. Metzger, Kouki Morizono, Aylin Bonifacino, Scott R. Penzak, Yi Ming Xie, Irvin S.Y. Chen, Jeffrey Bacon, Stephen G. Sestrich, Lawrence P. Szajek, Robert E. Donahue

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish
Pages (from-to)1212-1219
Number of pages8
JournalJournal of Nuclear Medicine
Volume47
Issue number7
StatePublished - 1 Jul 2006

Fingerprint

Molecular Imaging
Transgenes
Primates
Reporter Genes
Bromouracil
Thymidine Kinase
Human Herpesvirus 1
Genetic Therapy
Blood Vessels
Half-Life
Pharmacokinetics
Phosphorylation
1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil
Enzymes
Genes

Keywords

  • Br-FBAU
  • Gene therapy
  • Molecular imaging
  • Nonhuman primates
  • PET

Cite this

Sander, W. E., Metzger, M. E., Morizono, K., Bonifacino, A., Penzak, S. R., Xie, Y. M., ... Donahue, R. E. (2006). Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates. Journal of Nuclear Medicine, 47(7), 1212-1219.
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. / Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates. In: Journal of Nuclear Medicine. 2006 ; Vol. 47, No. 7. pp. 1212-1219.
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Sander, WE, Metzger, ME, Morizono, K, Bonifacino, A, Penzak, SR, Xie, YM, Chen, ISY, Bacon, J, Sestrich, SG, Szajek, LP & Donahue, RE 2006, 'Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates', Journal of Nuclear Medicine, vol. 47, no. 7, pp. 1212-1219.

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 journalArticle

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.

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KW - Nonhuman primates

KW - PET

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AN - SCOPUS:33747145289

VL - 47

SP - 1212

EP - 1219

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

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Sander WE, Metzger ME, Morizono K, Bonifacino A, Penzak SR, Xie YM et al. Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates. Journal of Nuclear Medicine. 2006 Jul 1;47(7):1212-1219.