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

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

UNT System College of Pharmacy

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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

Keywords

Br-FBAU
Gene therapy
Molecular imaging
Nonhuman primates
PET

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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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title = "Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates",

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.",

keywords = "Br-FBAU, Gene therapy, Molecular imaging, Nonhuman primates, PET",

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

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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 › peer-review

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

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JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 7

ER -

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

Abstract

Keywords

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