HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sander, W. E. Articles by Donahue, R. E. Search for Related Content PubMed PubMed Citation Articles by Sander, W. E. Articles by Donahue, R. E.

Noninvasive Molecular Imaging to Detect Transgene Expression of Lentiviral Vector in Nonhuman Primates

¹ Hematology Branch, National Heart, Lung, and Blood Institute, Rockville, Maryland; ² AIDS Institute, UCLA School of Medicine, Los Angeles, California; ³ Clinical Pharmacokinetics Research Laboratory, Pharmacy Department, NIH Clinical Center, Bethesda, Maryland; and ⁴ PET Imaging Section, NIH Clinical Center, Bethesda, Maryland

Correspondence: For correspondence or reprints contact: Robert E. Donahue, VMD, Hematology Branch, NHLBI, 5 Research Ct., Rockville, MD 20850. E-mail: donahuer{at}nhlbi.nih.gov Guest Editor: Sanjiv Gambhir

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-ß-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.

Key Words: ⁷⁶Br-FBAU • gene therapy • PET • nonhuman primates • molecular imaging

This article has been cited by other articles:

				M. Johnson, B. D.W. Karanikolas, S. J. Priceman, R. Powell, M. E. Black, H.-M. Wu, J. Czernin, S.-C. Huang, and L. Wu Titration of Variant HSV1-tk Gene Expression to Determine the Sensitivity of 18F-FHBG PET Imaging in a Prostate Tumor J. Nucl. Med., May 1, 2009; 50(5): 757 - 764. [Abstract] [Full Text] [PDF]

				C. Soulas, R. E. Donahue, C. E. Dunbar, D. A. Persons, X. Alvarez, and K. C. Williams Genetically Modified CD34+ Hematopoietic Stem Cells Contribute to Turnover of Brain Perivascular Macrophages in Long-Term Repopulated Primates Am. J. Pathol., May 1, 2009; 174(5): 1808 - 1817. [Abstract] [Full Text] [PDF]

				D. S. An, R. E. Donahue, M. Kamata, B. Poon, M. Metzger, S.-H. Mao, A. Bonifacino, A. E. Krouse, J.-L. Darlix, D. Baltimore, et al. Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates PNAS, August 7, 2007; 104(32): 13110 - 13115. [Abstract] [Full Text] [PDF]