Imaging of Gene Delivery and Expression

  • Carolyn Nichol
  • E. Edmund Kim


Recent advances in cell biology and genetic engineering have led to the identification of genes that control many disease states, including cancer, cystic fibrosis, sickle cell anemia, AIDS, and Parkinson’s disease. These discoveries have led to an increased understanding of the fundamental mechanisms of disease and to the development of genetically based therapies. Although new genes are being identified at the rate of approximately one new gene per day and progress is being made in the use of new gene therapies in animal studies and clinical trials, the primary method to test for gene expression involves tissue analysis. Tissue analysis is expensive, time consuming, painful, and subject to sampling errors. Only recently it has been possible to determine noninvasively if exogenous genes are being delivered to the diseased sites and if the exogenous protein is being expressed.


Single Photon Emission Compute Tomography Gene Therapy Gene Delivery Herpes Simplex Virus Type Thymidine Kinase 
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  1. 1.
    Ko S-C, Gotoh A, Thalmann GN, et al. Molecular therapy with recombinant p53 adenovirus in an androgen-independent, metastatic human prostate cancer model. Hum Gene Ther 1996;7: 1683–1691.PubMedCrossRefGoogle Scholar
  2. 2.
    Nguyen DM, Wiehle SA, Koch PE, et al. Delivery of the p53 tumor suppressor gene into lung cancer cells by an adenovirus/DNA complex. Can Gene Ther 1997;4:191–198.Google Scholar
  3. 3.
    Braun-Falco M, Doenecke A, Smola H, Hallek M. Efficient gene transfer into heman keratinocytes with recombinant adenoassociated virus vectors. Gene Ther 1999;6:432–441.PubMedCrossRefGoogle Scholar
  4. 4.
    Wiznerowicz M, Fong AZC, Mackiewicz A, Hawley RG. Double-copy bicistronic retroviral vector platform for gene therapy and tissue engineering: application to melanoma vaccine development. Gene Ther 1997;4:1061–1068.PubMedCrossRefGoogle Scholar
  5. 5.
    Hanania EG, Deisseroth AB. Serial transplantation shows that early hematopoietic precursor cells are transduced by MDR-1 retroviral vector in a mouse gene therapy model. Can Gene Ther 1994;1:21–25.Google Scholar
  6. 6.
    Blasberg R, Tjuvajev J. Herpes simplex virus thymidine kinase as a marker/reporter gene for PET imaging of gene therapy. Q J Nucl Med 1999;43:163–169.PubMedGoogle Scholar
  7. 7.
    Ross D, Kim B, Davidson B. Assessment of ganciclovir toxicity to experimental intracranial gliomas following recombinant adenoviralmediated transfer of the herpes simplex virus thymidine kinase gene by magnetic resonance imaging and proton magnetic resonance imaging. Clin Cancer Res 1995;1:651–657.PubMedGoogle Scholar
  8. 8.
    Schellingerhout D, Bogdanov A, Marecos E, Spear M, Breakefield X, Weissleder R. Mapping the in vivo distribution of herpes simplex virions. Hum Gene Ther 1998;9:1543–1549.PubMedCrossRefGoogle Scholar
  9. 9.
    Smaglik P. Viral vs. nonviral in gene therapy: which vector will prevail? Scientist 1998;12: 5–6.Google Scholar
  10. 10.
    Kuo PYP, Saltzman WM. Novel systems for controlled delivery of macromolecules. Crit Rev Eukaryotic Gene Expr 1996;6:59–73.CrossRefGoogle Scholar
  11. 11.
    Abdallah B, Sachs L, Demeneix BA. Non-viral gene transfer: applications in developmental biology and gene therapy. Biol Cell 1995;85:1–7.PubMedGoogle Scholar
  12. 12.
    Felgner PL. Nonviral strategies for gene therapy. Sci Am 1997;276:102–110.PubMedCrossRefGoogle Scholar
  13. 13.
    Crystal RG. Gene as the drug. Nat Med 1995; 1:15–17.PubMedCrossRefGoogle Scholar
  14. 14.
    Ledely F. Nonviral gene therapy: the promise of genes as pharmaceutical products. Hum Gene Ther 1995;6:1129–1144.CrossRefGoogle Scholar
  15. 15.
    Sochanik A, Szala S. On the strategy of using nonviral carriers in cancer gene therapy. Acta Biochim Pol 1996;43:295–300.Google Scholar
  16. 16.
    Zenke M, Steinlein P, Wagner E, Cotten M, Beug H, Birnstiel ML. Receptor-mediated endocytosis of transferrin-polycation conjugates: an efficient way to introduce DNA into hematopoietic cells. Proc NY Acad Sci 1990;87:3655–3659.CrossRefGoogle Scholar
  17. 17.
    Suzuki T, Shin B-C, Fujikura K, Matsuzaki T, Takata K. Direct gene transfer into rat liver cells by in vivo electroporation. FEBS Lett 1998;425:436–440.PubMedCrossRefGoogle Scholar
  18. 18.
    Yang J-P, Huang L. Direct gene transfer to mouse melanoma by intratumor injection of free DNA. Gene Ther 1996;3:542–548.PubMedGoogle Scholar
  19. 19.
    Wagner E, Zatloukal K, Cotten M, et al. Coupling of adenovirus to transferrinpolylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. Proc Natl Acad Sci USA 1992;89:6099–6103.PubMedCrossRefGoogle Scholar
  20. 20.
    Bonnekoh B, Greenhalgh D, Bundman D, et al. Adenoviral-mediated herpes simplex virusthymidine kinase gene transfer in vivo for treatment of experimental human melanoma. J Invest Dermatol 1996;106:1163–1168.PubMedCrossRefGoogle Scholar
  21. 21.
    Haberkorn U, Altmann A, Morr I, et al. Monitoring gene therapy with herpes simplex virus thymidine kinase in hepatoma cells: uptake of specific substrates. J Nucl Med 1997;38:287–294.PubMedGoogle Scholar
  22. 22.
    Moolten FL. Drug senstivity (“suicide genes”) for selective cancer chemotherapy. Cancer Gene Ther 1994;1:279–287.PubMedGoogle Scholar
  23. 23.
    Zinn K, Douglas J, Smyth C, et al. Imaging and tissue biodistribution of 99mTc-labeled adenovirus knob. Gene Ther 1998;5:798–808.PubMedCrossRefGoogle Scholar
  24. 24.
    Harrington KJ, Peters AM, Mohammadtaghi S, Glass D, Epenetos AA, Stewart JSW. Biodistribution and pharmacokinetics of In-111-labels Stealth liposomes in patients with solid tumours. J Nucl Med 1996;37:54P.Google Scholar
  25. 25.
    Nichol CA, Yang D, Humphrey W, et al. Biodistribution and imaging of polyethyleneimine—a gene delivery agent. Drug Delivery 1999;6: 187–194.CrossRefGoogle Scholar
  26. 26.
    Weibe L, Knaus E, Morin K. Radiolabelled pyrimidine nucleosides to monitor the expression of HSV-1 thymidine kinase in gene therapy. Nucleosides Nucleotides 1999;18:1065–1066.CrossRefGoogle Scholar
  27. 27.
    Tjuvajev J, Joshi R, Kennedy J, et al. Gamma camera imaging of HSV-tk gene expression with [131I]-FIAU: clinical applications in gene therapy. J Nucl Med 1996;37:53P.Google Scholar
  28. 28.
    Urbain JLC, Shore SK, Vekemans MC, et al. Scintigraphic imaging of oncogenes with antisense probes: does it make sense? Eur J Nucl Med 1995;22:499–504.PubMedCrossRefGoogle Scholar
  29. 29.
    Gambhir S, Barrio J, Wu L, et al. Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabled gancyclovir. J Nucl Med 1998;39:2003–2011.PubMedGoogle Scholar
  30. 30.
    Morin K, Knaus E, Wiebe L. Non-invasive scintigraphic monitoring of gene expression in a HSV- 1 thymidine kinase gene therapy. Nucl Med Commun 1997;18:599–605.PubMedCrossRefGoogle Scholar
  31. 31.
    Poptani H, Puumalainen A, Grohn O, et al. Monitoring thymidine kinase and ganciclovir-induced changes in rat malignant glioma in vivo by nuclear magnetic resonance imaging. Cancer Gene Ther 1998;5:101–109.PubMedGoogle Scholar
  32. 32.
    Tjuvajev J, Avril N, Oku T, et al. Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. Cancer Res 1998;58:4333–4341.PubMedGoogle Scholar
  33. 33.
    Huard J, Lochmuller H, Acsadi G, Jani A, Massie B, Karpati G. The route of administration is a major determinant of the transduction efficiency of rat tissues by adenoviral recombinants. Gene Ther 1995;2:107–115.PubMedGoogle Scholar
  34. 34.
    Kass-Eisler A, Falck-Pederson E, Elfenbein DH, Alvira M, Buttrick PM, Leinwand LA. The impact of developmental stage, route of administration and the immune system on adenovirusmediated gene transfer. Gene Ther 1994;1:395–402.PubMedGoogle Scholar
  35. 35.
    Timmermans J, Moes AJ. Factors controlling the buoyancy and gastric retention capabilities of floating matrix capsules: new data for reconsidering the controversy. J Pharm Sci 1994;83:18–24.PubMedCrossRefGoogle Scholar
  36. 36.
    Tjuvajev JG, Stockhammer G, Desai R, et al. Imaging the expression of transfected gene in vivo. Cancer Res 1995;55:6126–6132.PubMedGoogle Scholar
  37. 37.
    Srinivasan A, Gambhi S, Green LA, et al. A PET reporter gene (PRG)/PET reporter probe (PRP) technology for repeatedly imaging gene expression in living animals. J Nucl Med 1996;37:107P.Google Scholar
  38. 38.
    Green LA, Gambhir SS, Barrio JR, et al. Tracer kinetic modeling of 8-(F-18)-fluoro-ganciclovir PET data: a new tracer for measuring reporter gene expression. J Nucl Med 1998;39:10p.Google Scholar
  39. 39.
    Goldman S, Monclus M, Cool V, et al. A novel PET tracer for evaluation of gene therapy. J Nucl Med 1996;37:53P.Google Scholar
  40. 40.
    Alauddin M, Conti P, Mazza S, Hamzeh F, Lever J. 9-[(3-[18F]-Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]-FHPG): a potential imaging agent of viral infection and gene therapy using PET. Nucl Med Biol 1996;23: 787–792.PubMedCrossRefGoogle Scholar
  41. 41.
    Alauddin M, Conti P. Synthesis and preliminary evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG): a new potential imaging agent for viral infection and gene therapy using PET. Nucl Med Biol 1998;23: 175–180.CrossRefGoogle Scholar
  42. 42.
    Alauddin M, Shahinian A, Kundu R, Gordon E, Conti P. Evaluation of 9-[(3-18F-fluoro1-hydroxy-2-propoxy)methyl]guanine ([18F]-FHPG) in vitro and in vivo as a probe for PET imaging of gene incorporation and expression in tumors. Nucl Med Biol 1999;26:371–376.PubMedCrossRefGoogle Scholar
  43. 43.
    Raben D, Buchsbaum DJ, Khazaeli MB, et al. Enhancement of radiolabeled antibody binding and tumor localization through adenoviral transduction of the human carcinoembryonic antigen gene. Gene Ther 1996;3:567–580.PubMedGoogle Scholar
  44. 44.
    MacLaren DC, Gambhir SS, Satyamurthy N, et al. Repetitive, non-invasive imaging of the dopamine D-2 receptor as a reporter gene in living animals. Gene Ther 1999;6:785–791.PubMedCrossRefGoogle Scholar
  45. 45.
    Mandell R, Mandell L, Link C. Radioisotope concentrator gene therapy using the sodium/ iodide symporter gene. Cancer Res 1999;59:661–668.PubMedGoogle Scholar
  46. 46.
    Kayyem J, Kumar R, Fraser S, Meade T. Receptor-targeted co-transport of DNA and magnetic resonance contrast agents. Chem Biol 1995;2:615–620.PubMedCrossRefGoogle Scholar
  47. 47.
    de Marko G, Bogdanov A, Marecos E, Moore A, Simonova M, Weissleder R. MR imaging of gene delivery to the central nervous system with an artificial vector. Radiology 1998;208:65–71.Google Scholar
  48. 48.
    Weissleder R, Simonova M, Bogdanova A, Bredow S, Enochs W, Bogdanov A. MR imaging and scintigraphy of gene expression through melanin induction. Radiology 1997;204:425–429.PubMedGoogle Scholar
  49. 49.
    Moore A, Basilion JP, Chiocca EA, Weissleder R. Measuring transferrin receptor gene expression by NMR imaging. Biochim Biophys Acta 1998; 1402:236–249.CrossRefGoogle Scholar
  50. 50.
    Contag PR, Olomu IN, Stevenson DK, Contag CH. Bioluminescent indicators in living animals. Nat Med 1998;4:245–247.PubMedCrossRefGoogle Scholar
  51. 51.
    Beraron D, Contag P, Contag C. Imaging brain structure and function, infection and gene expression in the body using light. Philos Trans R Soc Lond Ser B Biol Sci 1997;352:755–761.CrossRefGoogle Scholar
  52. 52.
    Edinger M, Sweeny TJ, Tucker AA, et al. Non-invasive assessment of tumor cell proliferation in animal models. Neoplasia 1999;1:303–310.PubMedCrossRefGoogle Scholar
  53. 53.
    Kan X, Liu T-J. Video microscopy of tumor metastasis: using the green fluorescent protein (GFP) gene as a cancer-cell-labeling system. Clin Exp Metastas 1999;17:49–55.CrossRefGoogle Scholar
  54. 54.
    Cordobes M, Starzec A, Delmon-Moingeon L, et al. Technetium-99m-sestamibi uptake by human benign and malignant breast tumor cells: correlation with mdr gene expression. J Nucl Med 1996;37:286–289.PubMedGoogle Scholar
  55. 55.
    Crankshaw CL, Marmion M, Luker GD, et al. Novel technetium(III)-Q complexes for functional imaging of multidrug resistance (MDR1) P-glycoprotein. J Nucl Med 1998;39:77–86.PubMedGoogle Scholar

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© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Carolyn Nichol
  • E. Edmund Kim

There are no affiliations available

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