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Chen IY, Wu JC, Min JJ, et al. Micro-positron emission tomography imaging of cardiac gene expression in rats using bicistronic adenoviral vector-mediated gene delivery. Circulation. 2004;109(11):1415-20doi: 10.1161/01.CIR.0000121727.59564.5B.
Chen, I. Y., Wu, J. C., Min, J. J., Sundaresan, G., Lewis, X., Liang, Q., Herschman, H. R., & Gambhir, S. S. (2004). Micro-positron emission tomography imaging of cardiac gene expression in rats using bicistronic adenoviral vector-mediated gene delivery. Circulation, 109(11), 1415-20. https://doi.org/10.1161/01.CIR.0000121727.59564.5B
Chen, Ian Y, et al. "Micro-positron emission tomography imaging of cardiac gene expression in rats using bicistronic adenoviral vector-mediated gene delivery." Circulation vol. 109,11 (2004): 1415-20. doi: https://doi.org/10.1161/01.CIR.0000121727.59564.5B
Chen IY, Wu JC, Min JJ, Sundaresan G, Lewis X, Liang Q, Herschman HR, Gambhir SS. Micro-positron emission tomography imaging of cardiac gene expression in rats using bicistronic adenoviral vector-mediated gene delivery. Circulation. 2004 Mar 23;109(11):1415-20. doi: 10.1161/01.CIR.0000121727.59564.5B. Epub 2004 Mar 08. PMID: 15007006; PMCID: PMC4154818.
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Circulation. 2004 Mar 23;109(11):1415-20. doi: 10.1161/01.CIR.0000121727.59564.5B. Epub 2004 Mar 08.

Micro-positron emission tomography imaging of cardiac gene expression in rats using bicistronic adenoviral vector-mediated gene delivery.

Circulation

Ian Y Chen, Joseph C Wu, Jung-Jun Min, Gobalakrishnan Sundaresan, Xiaoman Lewis, Qianwa Liang, Harvey R Herschman, Sanjiv S Gambhir

Affiliations

  1. Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, Calif 94305-5427, USA.

PMID: 15007006 PMCID: PMC4154818 DOI: 10.1161/01.CIR.0000121727.59564.5B

Abstract

BACKGROUND: We have previously validated the use of micro-positron emission tomography (microPET) for monitoring the expression of a single PET reporter gene in rat myocardium. We now report the use of a bicistronic adenoviral vector (Ad-CMV-D2R80a-IRES-HSV1-sr39tk) for linking the expression of 2 PET reporter genes, a mutant rat dopamine type 2 receptor (D2R80a) and a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk), with the aid of an internal ribosomal entry site (IRES).

METHODS AND RESULTS: Rat H9c2 cardiomyoblasts transduced with increasing titers of Ad-CMV-D2R80a-IRES-HSV1-sr39tk (0 to 2.5x10(8) pfu) were assayed 48 hours later for reporter protein activities, which were found to correlate well with viral titer (r2=0.96, P<0.001 for D2R80A; r2=0.98, P<0.001 for HSV1-sr39TK) and each other (r2=0.97; P<0.001). Experimental (n=8) and control (n=6) athymic rats underwent intramyocardial injection of up to 2x10(9) pfu of Ad-CMV-D2R80a-IRES-HSV1-sr39tk and saline, respectively. Forty-eight hours later and weekly thereafter, rats were assessed for D2R80a-dependent myocardial accumulation of 3-(2-[18F]fluoroethyl)spiperone ([18F]-FESP) and HSV1-sr39tk-dependent sequestration of 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]-FHBG) using microPET. Longitudinal [18F]-FESP and [18F]-FHBG imaging of experimental rats revealed a good correlation between the cardiac expressions of the 2 PET reporter genes (r2=0.73; P<0.001). The location of adenovirus-mediated transgene expression, as inferred from microPET images, was confirmed by ex vivo gamma counting of explanted heart.

CONCLUSIONS: The IRES-based bicistronic adenoviral vector can potentially be used in conjunction with PET for indirect imaging of therapeutic gene expression by replacing 1 of the 2 PET reporter genes with a therapeutic gene of choice.

References

  1. Circulation. 1996 Sep 15;94(6):1394-401 - PubMed
  2. ILAR J. 2001;42(3):219-32 - PubMed
  3. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1536-41 - PubMed
  4. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2333-8 - PubMed
  5. Gene Ther. 1995 Mar;2(2):107-15 - PubMed
  6. Curr Opin Mol Ther. 2001 Oct;3(5):454-63 - PubMed
  7. Biol Psychiatry. 2000 Sep 1;48(5):337-48 - PubMed
  8. Semin Nucl Med. 2001 Oct;31(4):312-20 - PubMed
  9. Nat Med. 2000 Aug;6(8):933-7 - PubMed
  10. Gene Ther. 2001 Oct;8(19):1490-8 - PubMed
  11. Gene Ther. 1999 May;6(5):785-91 - PubMed
  12. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2785-90 - PubMed
  13. Circulation. 2002 Jul 30;106(5):631-6 - PubMed
  14. J Nucl Med. 1998 Apr;39(4):729-34 - PubMed
  15. Circulation. 2002 Jul 9;106(2):180-3 - PubMed
  16. Circulation. 2000 Aug 29;102(9):948-50 - PubMed
  17. Nature. 2002 Jan 10;415(6868):234-9 - PubMed

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