Skip to main content
SpringerLink
Log in

Imaging Gene Expression in the Brain with Peptide Nucleic Acid (PNA) Antisense Radiopharmaceuticals and Drug Targeting Technology

  • Chapter
Peptide Nucleic Acids, Morpholinos and Related Antisense Biomolecules

Part of the book series: Medical Intelligence Unit ((MIUN))

Abstract

Antisense oligomers are potential pharmaceutical and radiopharmaceutical agents that can be used to modulate and image gene expression. Progress with in vivo gene targeting using antisense-based therapeutics has been slower than expected during the last decade, owing to poor trans-cellular delivery of antisense agents. This chapter suggests that if antisense pharmacology is merged with drug targeting technology, then membrane barriers can be circumvented and antisense agents can be delivered to tissues in vivo. Without the application of drug targeting, the likelihood of success for an antisense drug development program is low, particularly for the brain which is protected by the blood-brain barrier (BBB). Among the different classes of antisense agents, peptide nucleic acids (PNA) present advantages for in vivo applications over conventional and modified oligodeoxynucleotides (ODN), including phosphorothioates (PS)-ODN. Some advantages of PNAs include their electrically neutral backbone, low toxicity to neural cells, resistance to nucleases and peptidases, and lack of bind-ing to plasma proteins. PNAs are poorly transported through cellular membranes, including the BBB and the brain cell membrane (BCM). Because the mRNA target for the antisense agent lies within the cytosol of the target cell, the BBB and the BCM must be circumvented in vivo, which is possible with the use of chimeric peptide drug targeting technology. Chimeric peptides are formed by conjugation of a nontransportable drug, such as a PNA, to a drug delivery vector. The vector undergoes receptor-mediated transcytosis (RMT) through the BBB and receptor-mediated endocytosis through the BCM in vivo. When labeled with a radioisotope (e.g., 125I or 111In), the antisense chimeric peptide provides imaging of gene expression in the brain in vivo in a sequence-specific manner. Further development of antisense radio-pharmaceutical agents may allow for in vivo imaging of genes in pathological states, and may provide tools for the analysis of novel genes with functional genomics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Boado RJ. Antisense drug delivery through the blood-brain barrier. Adv Drug Deliv Rev 1995;15:73–107.

    Article  CAS  Google Scholar 

  2. Boado RJ, Tsukamoto H, Pardridge WM. Drug delivery of antisense molecules to the brain for treatment of Alzheimer’s disease and cerebral AIDS. J Pharm Sci 1998;87:1308–1315.

    Article  PubMed  CAS  Google Scholar 

  3. Haque N, Isacson O. Antisense gene therapy for neurodegenerative disease? Exp Neurol 1997;144:139–146.

    Article  PubMed  CAS  Google Scholar 

  4. Weiss B, Davidkova G, Zhang S-P. Antisense strategies in neurobiology. Neurochem 1997;31:321–348.

    Article  CAS  Google Scholar 

  5. Venter JC et al. The sequence of the human genome. Science 2001;291:1304–1351.

    Article  PubMed  CAS  Google Scholar 

  6. Lander ES et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860–921.

    Article  PubMed  CAS  Google Scholar 

  7. Chen TL, Miller PS, Ts’o PO et al. Disposition and metabolism of oligodeoxynucleoside methylphosphonate following a single i.v. injection in mice. Drug Metab Dispos 1990;18:815–818.

    PubMed  CAS  Google Scholar 

  8. Vlassov VV, Yakubov LA. Oligonucleotides in cells and organisms: Pharmacological considerations. In: Wickstrom E, ed. Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS. Wiley-Liss, NY: 1991:243–266.

    Google Scholar 

  9. Zendegui JG, Vasquez KM, Tinsley JH et al. In vivo stability and kinetics of absorption and disposition of 3′ phosphopropyl amine oligonucleotides. Nucleic Acids Res 1992;20:307–314.

    Article  PubMed  CAS  Google Scholar 

  10. Tavitian B, Terrazzino S, Kuhnast B et al. In vivo imaging of oligonucleotides with positron emission tomography. Nat Med 1998;4:467–471.

    Article  PubMed  CAS  Google Scholar 

  11. Wu D, Boado RJ, Pardridge WM. Pharmacokinetics and blood-brain barrier transport of [3H]-biotinylated phosphorothioate oligodeoxynucleotide conjugated to a vector-mediated drug de-livery system. J Pharmacol Exp Ther 1996;. 276:206–211.

    PubMed  CAS  Google Scholar 

  12. Brightman MW, Klatzo I, Olsson Y et al. The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci 1970;10:215–239.

    Article  PubMed  CAS  Google Scholar 

  13. Reynolds MA, Arnold Jr LJ, Almazan MT et al. Triple-strand-forming methylphosphonate oligodeoxynucleotides targeted to mRNA efficiently block protein synthesis. Proc Natl Acad Sci USA 1994;91:12433–12437.

    Article  PubMed  CAS  Google Scholar 

  14. Crooke ST. Progress toward oligonucleotide therapeutics: Pharmacodynamic properties. FASEB J 1993;7:533–539.

    PubMed  CAS  Google Scholar 

  15. Gao WY, Han FS, Storm C et al. Phosphorothioate oligonucleotides are inhibitors of human DNA polymerases and RNase H: Implications for antisense technology. Mol Pharmacol 1992;41:223–229.

    PubMed  CAS  Google Scholar 

  16. Stein CA, Cheng YC. Antisense oligonucleotides as therapeutic agents—is the bullet really magical? Science 1993;261:1004–1012.

    Article  PubMed  CAS  Google Scholar 

  17. Nutt SL, Bronchain OJ, Hartley KO et al. Comparison of morpholino based translational inhibition during the development of Xenopus laevis and Xenopus tropicalis. Genesis 2001;30:110–113.

    Article  PubMed  CAS  Google Scholar 

  18. Crouch RJ, Dirksen ML. Ribonucleases H. In: Linn SM, Roberts RJ, eds. Nucleases. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1982:211–241.

    Google Scholar 

  19. Mollegaard NE, Buchardt O, Egholm M et al. Peptide nucleic acid. DNA strand displacement loops as artificial transcription promoters. Proc Natl Acad Sci USA 1994;91:3892–3895.

    Article  PubMed  CAS  Google Scholar 

  20. Schoenberg BS. The epidemiology of nervous system tumors. In: Walker D, ed. Oncology of the Nervous System. Martinus Nijhoff, Boston: 1983.

    Google Scholar 

  21. Simpson JR, Horton J, Scott C et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: Results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 1993;26:239–244.

    PubMed  CAS  Google Scholar 

  22. Galanis E, Buckner JC, Dinapoli RP et al. Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results. J Neurosurg 1998;89:425–430.

    Article  PubMed  CAS  Google Scholar 

  23. Herfarth KK, Gutwein S, Debus J. Postoperative radiotherapy of astrocytomas. Semin Surg Oncol 2001;20:13–23.

    Article  PubMed  CAS  Google Scholar 

  24. Bredel M. Anticancer drug resistance in primary human brain tumors. Brain Res Rev 2001;35:161–204.

    Article  PubMed  CAS  Google Scholar 

  25. Giese A, Westphal M. Treatment of malignant glioma: A problem beyond the margins of resection. J Cancer Res Clin Oncol 2001;127:217–225.

    Article  PubMed  CAS  Google Scholar 

  26. Westphal M, Herrmann HD. Growth factor biology and oncogene activation in human gliomas and their implications for specific therapeutic concepts. Neurosurgery 1989;25:681–694.

    Article  PubMed  CAS  Google Scholar 

  27. Ho PTC, Parkinson DR. Antisense oligonucleotides as therapeutics for malignant diseases. Semin Oncol 1997;24:187–202.

    PubMed  CAS  Google Scholar 

  28. Nitta T, Sato K. Specific inhibition of c-sis protein synthesis and cell proliferation with antisense oligodeoxynucleotides in human glioma cells. Neurosurgery 1994;34:309–315.

    Article  PubMed  CAS  Google Scholar 

  29. Guha A, Dashner K, Black PM et al. Expression of PDGF and PDGF receptors in human astrocytoma operation specimens supports the existence of an autocrine loop. Int J Cancer 1995;60:168–173.

    PubMed  CAS  Google Scholar 

  30. Smith JS, Jenkins RB. Genetic alterations in adult diffuse glioma: Occurrence, significance, and prognostic implications. Front Biosci 2000;5:213–231.

    Google Scholar 

  31. Murphy PR, Sato Y, Knee RS. Phosphorothioate antisense 7oligonucleotides against basic fibroblast growth factor inhibit anchorage-dependent and anchorage-independent growth of a malignant glioblastoma cell line. Mol Endocrinol 1992;6:877–884.

    Article  PubMed  CAS  Google Scholar 

  32. Behl C, Winkler J, Bogdahn U et al. Autocrine growth regulation in neuroectodermal tumors as detected with oligodeoxynudeotide antisense molecules. Neurosurgery 1993;78:944–951.

    Article  Google Scholar 

  33. Kurihara A, Pardridge WM. Imaging brain tumors by targeting peptide radiopharmaceuticals through the blood-brain barrier. Cancer Res 1999;54:6159–6163.

    Google Scholar 

  34. Katzman R. Alzheimer’s disease. N Engl J Med 1986;314:964–973.

    Article  PubMed  CAS  Google Scholar 

  35. Selkoe DJ. The molecular pathology of Alzheimer’s disease. Neuron 1991;6:487–498.

    Article  PubMed  CAS  Google Scholar 

  36. Kang J, Lemaire HG, Unterbeck A et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 1987;325:733–736.

    Article  PubMed  CAS  Google Scholar 

  37. Robakis NK, Ramakrishna N, Wolfe G et al. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci USA 1987;84:4190–4194.

    Article  PubMed  CAS  Google Scholar 

  38. Tanzi RE, Gusella JF, Watkins PC et al. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic likage near the Alzheimer locus. Science 1987;235:880–884.

    Article  PubMed  CAS  Google Scholar 

  39. Jacobsen SJ, Blume AJ, Vitek MP. Quantitative measurement of alternatively spliced amyloid pre-cursor protein mRNA expression in Alzheimer’s disease and normal brain by S1 nuclease protection analysis. Neurobiol Aging 1991;12:585–592.

    Article  PubMed  CAS  Google Scholar 

  40. Games D, Adams D, Alessandrini R et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta amyloid precursor protein. Nature 1995;373:523–527.

    Article  PubMed  CAS  Google Scholar 

  41. Martin JB, Gusella JF. Huntington’s disease. Pathogenesis and management. N Engl J Med 1989;315:1267–1276.

    Google Scholar 

  42. Huntington’s Disease Collaborative Research Group. A novel gene containing a trinudeotide re-peat that is expanded and unstable on Huntington’s disease chromosome. Cell 1993;72:971–983.

    Article  Google Scholar 

  43. Davies SW, Turmaine M, Cozens BA et al. Formation of neuronal intranuclear inclusions under-lies then neurological dysfunction in mice transgenic for the HD mutation. Cell 1997;90:537–548.

    Article  PubMed  CAS  Google Scholar 

  44. Reddy PH, Williams M, Tagle DA. Recent advances in understanding the pathogenesis of Huntington’s disease. Trends Neurosci 1999;22:248–255.

    Article  PubMed  CAS  Google Scholar 

  45. White JK, Auerbach W, Duyao MP et al. Huntingtin is required for neurogenesis and is not impaired by the Huntington’s disease. Nat Genet 1997;17:404–410.

    Article  PubMed  CAS  Google Scholar 

  46. Boado RJ, Kazantsev A, Apostol BL et al. Antisense-mediated down-regulation of the human Huntingtin gene. J Pharmacol Exp Ther 2000;295:239–243.

    PubMed  CAS  Google Scholar 

  47. Navia BA, Jordan BD, Price RW. The AIDS dementia complex: I. Clinical features. Ann Neurol 1986;19:517–524.

    Article  PubMed  CAS  Google Scholar 

  48. Navia BA, Cho ES, Petito CK et al. The AIDS dementia complex: II. Clinical features. Ann Neurol 1986;19:525–535.

    Article  PubMed  CAS  Google Scholar 

  49. Kaul M, Garden GA, Lipton SA. Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 2001;410:988–994.

    Article  PubMed  CAS  Google Scholar 

  50. Resnick L, Berger JR, Shapshak P et al. Early penetration of the blood-brain barrier by HIV. Neurol 1988;38:9–14.

    CAS  Google Scholar 

  51. Weisberg LA. Neurologic abnormalities in human immunodeficiency virus infection. South Med J 2001;94:266–275.

    PubMed  CAS  Google Scholar 

  52. Atwood WJ, Berger JR, Kaderman R et al. Human immunodeficiency virus type 1 infection of the brain. Clin Microbiol Rev 1993;6:339–366.

    PubMed  CAS  Google Scholar 

  53. Bussolino F, Mitola S, Serini G et al. Interactions between endothelial cells and HIV-1. Int J Biochem Cell Biol 2001;33:371–390.

    Article  PubMed  CAS  Google Scholar 

  54. Perry VH, Gordon S. Modulation of CD4 antigen on macrophages and microglia in rat brain. J Exp Med 1987; 166:1138–1143.

    Article  PubMed  CAS  Google Scholar 

  55. Terasaki T, Pardridge WM. Restricted transport of 3′-azido-3′-deoxythymidine and dideoxynucleosides through the blood-brain barrier. J Infect Dis 1988; 158:630–632.

    PubMed  CAS  Google Scholar 

  56. Pomerantz RJ. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. Biomed Pharmacother 2001; 55:7–15.

    Article  PubMed  CAS  Google Scholar 

  57. Agrawal S. Antisense oligonucleotides: A possible approach for chemotherapy of AIDS. In: Wickstrom E, ed. Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS. Wiley-Liss, New York: 1991:143–158.

    Google Scholar 

  58. Narayanan R, Akhtar S. Antisense therapy. Curr Opin Oncol 1996; 8:509–515.

    Article  PubMed  CAS  Google Scholar 

  59. Galderisi U, Cascino A, Giordano A. Antisense oligonucleotides as therapeutic agents. J Cell Physiol 1999; 181:251–257.

    Article  PubMed  CAS  Google Scholar 

  60. Lisziewicz J, Sun D, Weichold FF et al. Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells. Proc Natl Acad Sci USA 1994; 91:7942–7946.

    Article  PubMed  CAS  Google Scholar 

  61. Pardridge WM, Boado RJ, Kang YS. Vector-mediated delivery of a polyamide (“peptide”) nucleic acid analogue through the blood-brain barrier in vivo. Proc Natl Acad Sci USA 1995; 92:5592–5596.

    Article  PubMed  CAS  Google Scholar 

  62. Croix BS, Rago C, Velculescu V et al. Genes expressed in human tumor endothelium. Science 2000; 289:1197–1202.

    Article  Google Scholar 

  63. Li JY, Boado RJ, Pardridge WM. Blood-brain barrier genomics. J Cereb Blood Flow Metab 2001; 21:61–68.

    Article  PubMed  CAS  Google Scholar 

  64. Pardridge WM. Isolated brain capillaries: An in vitro model of blood-brain barrier research. In: Pardridge WM, ed. An Introduction to the Blood-Brain Barrier: Methodology and Biology. Cambridge University Press, 1998:49–61.

    Google Scholar 

  65. Boado RJ. Molecular Biology of Brain Capillaries. In: Pardridge WM, ed An Introduction to the Blood-Brain Barrier: Methodology and Biology. Cambridge University Press, 1998:151–162.

    Google Scholar 

  66. Pardridge WM. Brain Drug Targeting: The Future of Brain Drug Development. Cambridge: Cambridge University Press, 2001:1–370.

    Google Scholar 

  67. Boado RJ, Pardridge WM. Complete protection of antisense oligonucleotides against serum nuclease degradation by an avidin-biotin system. Bioconjugate Chem 1994; 3:519–523.

    Article  Google Scholar 

  68. Boado RJ, Pardridge WM. Complete inactivation of target mRNA by biotinylated antisense oligodeoxynucleotide-avidin conjugates. Bioconjugate Chem 1994; 5:406–410.

    Article  CAS  Google Scholar 

  69. Kang YS, Boado RJ, Pardridge WM. Pharmacokinetics and organ clearance of a 3′-biotinylated, internally [32P]-labeled phosphodiester oligodeoxynucleotide coupled to a neutral avidin/monoclonal antibody conjugate. Drug Metab Dispos 1995; 23:55–59.

    PubMed  CAS  Google Scholar 

  70. Boado RJ, Kang YS, Wu D et al. Rapid plasma clearance and metabolism in vivo of a phosphorothioate oligodeoxynucleotide with a single, internal phosphodiester bond. Drug Metab Dispos 1995; 23:1297–1300.

    PubMed  CAS  Google Scholar 

  71. Wojcik WJ, Swoveland P, Zhang X et al. Chronic intrathecal infusion of phosphorothioate or phosphodiester antisense oligonucleotides against cytokine responsive gene-2/IP-10 in experimental allergic encephalomyelitis of lewis rat. J Pharmacol Exp Ther 1996; 278:404–410.

    PubMed  CAS  Google Scholar 

  72. Chiasson BJ, Armstrong JN, Hooper ML et al. The application of antisense oligonucleotide technology to the brain: Some pitfalls. Cell Mol Neurobiol 1994; 14:507–521.

    Article  PubMed  CAS  Google Scholar 

  73. Perez JR, LI Y, Stein CA et al. Sequence independent induction of Sp1 transcription factor activity by phosphorothioate oligonucleotides. Proc Natl Acad Sci USA 1994; 91:5959–5961.

    Article  Google Scholar 

  74. Nielsen PE, Egholm M, Buchardt O. Peptide nucleic acid (PNA). A DNA mimic with a peptide backbone. Bioconjugate Chem 1994; 5:3–7.

    Article  CAS  Google Scholar 

  75. Shi N, Boado RJ, Pardridge WM. Antisense imaging of gene expression in the brain in vivo. Proc Natl Acad Sci USA 2000; 97:14709–14714.

    Article  PubMed  CAS  Google Scholar 

  76. Grzanna R, Dubin JR, Dent GW et al. Intrastriatal and intraventricular injections of oligodeoxynucleotides in the rat brain: Tissue penetration, intracellular distribution and c-fos antisense effects. Brain Res Mol brain Res 1998; 63:35–52.

    Article  PubMed  CAS  Google Scholar 

  77. Pardridge WM. Drug delivery to the brain. J Cereb Blood Flow Metab 1997; 17:713–731.

    Article  PubMed  CAS  Google Scholar 

  78. Tyler BM, Jansen K, McCormick DJ et al. Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression. Proc Natl Acad Sci USA 1999; 96:7053–7058.

    Article  PubMed  CAS  Google Scholar 

  79. Skarlatos S, Yoshikawa T, Pardridge WM. Transport of [125I] transferrin through the rat blood-brain barrier in vivo. Brain Res 1995; 683:164–171.

    Article  PubMed  CAS  Google Scholar 

  80. Lee HJ, Engelhardt B, Lesley J et al. Targeting rat anti-mouse transferrin receptor monoclonal antibodies through the blood-brain barrier in the mouse. J Pharmacol Exp Ther 2000; 292:1048–1052.

    PubMed  CAS  Google Scholar 

  81. Huwyler J, Pardridge WM. Examination of blood-brain barrier transferrin receptor by confocal fluorescent microscopy of unfixed isolated rat brain capillaries. J Neurochem 1998; 70:883–886.

    Article  PubMed  CAS  Google Scholar 

  82. Mash DC, Pablo J, Flynn DD et al. Characterization and distribution of transferrin receptors in the rat brain. J Neurochem 1990; 55:1972–1979.

    Article  PubMed  CAS  Google Scholar 

  83. Wu D, Pardridge WM. CNS pharmacologic effect in conscious rats after intravenous injection of a biotinylated vasoactive intestinal peptide analogue coupled to a blood-brain barrier drug delivery system. J Pharmacol Exp Ther 1996; 279:77–83.

    PubMed  CAS  Google Scholar 

  84. Bickel U, Yoshikawa T, Landaw EM et al. Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery. Proc Natl Acad Sci USA 1993; 90:2618–2622.

    Article  PubMed  CAS  Google Scholar 

  85. Wu D, Pardridge WM. Neuroprotection with noninvasive neurotrophin delivery to the brain. Proc Natl Acad Sci USA 1999; 96:254–259.

    Article  PubMed  CAS  Google Scholar 

  86. Sakane T, Pardridge WM. Carboxyl-directed pegylation of brain-derived neurotrophic factor markedly reduces systemic clearance with minimal loss of biologic activity. Pharm Res 1997; 14:1085–1091.

    Article  PubMed  CAS  Google Scholar 

  87. Pardridge WM, Kang YS, Buciak JL et al. Human insulin receptor monoclonal antibody undergoes high affinity binding to human brain capillaries in vitro and rapid transcytosis through the blood-brain barrier in vivo in the primate. Pharm Res 1995; 12:807–816.

    Article  PubMed  CAS  Google Scholar 

  88. Coloma MJ, Lee HJ, Kurihara A et al. Transport across the primate blood-brain barrier of a genetically engineered chimeric monoclonal antibody to the human insulin receptor. Pharm Res 2000; 17:266–274.

    Article  PubMed  CAS  Google Scholar 

  89. Penichet ML, Kang YS, Pardridge WM et al. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: Initial applications in anti-HIV antisense drug delivery to the brain. J Immunol 1999; 163:4421–4426.

    PubMed  CAS  Google Scholar 

  90. Li JY, Sugimura K, Boado RJ et al. Genetically engineered brain drug delivery vectors: Cloning, expression and in vivo application of an anti-transferrin receptor single chain antibody-streptavidin fusion gene and protein. Protein Eng 1999; 12:787–796.

    Article  PubMed  CAS  Google Scholar 

  91. Zhang Y, Pardridge WM. Rapid transferrin efflux from brain to blood across the blood-brain barrier. J Neurochem 2001; 76:1597–1600.

    Article  PubMed  CAS  Google Scholar 

  92. Zhang Y, Pardridge WM. Mediated efflux of IgG molecules from brain to blood across the blood-brain barrier. J Neuroimmunol 2001; 114:168–172.

    Article  PubMed  CAS  Google Scholar 

  93. Vrethem M, Henriksson A, Malm C et al. Ig-secreting cells pass the blood-brain barrier: Studies on κ and λ light chain secreting cells in plasma cell dyscrasia. J Neuroimmunol 1992; 41:189–194.

    Article  PubMed  CAS  Google Scholar 

  94. Kobori N, Imahori Y, Mineura K et al. Visualization of mRNA expression in CNS using 11C-labeled phosphorothioate oligodeoxynucleotide. Neuroreport 1999; 10:2971–2974.

    Article  PubMed  CAS  Google Scholar 

  95. de Smidt PC, Le Doan T, de Falco S et al. Association of antisense oligonucleotides with lipoproteins prolongs the plasma half-life and modifies the tissue distribution. Nucleic Acids Res 1991; 19:4695–4700.

    Article  PubMed  Google Scholar 

  96. Krieg AM, Tonkinson J, Matson S et al. Modification of antisense phosphodiester oligodeoxynucleotides by a 5′ cholesteryl moiety increases cellular association and improves efficacy. Proc Natl Acad Sci USA 1993; 90:1048–1052.

    PubMed  CAS  Google Scholar 

  97. Pardridge WM. CNS drug design based on principles of blood-brain barrier transport. J Neurochem 1998; 70:1781–1792.

    Article  PubMed  CAS  Google Scholar 

  98. Rebert CS, Matteucci MJ, Pryor GT. Acute interactive pharmacologic effects of inhaled toluene and dichloromethane on rat brain electrophysiology. Pharmacol Biochem Behav 1990; 36:351–365.

    Article  PubMed  CAS  Google Scholar 

  99. Brink JJ, Stein DG. Pemoline levels in brain: Enhancement by dimethyl sulfoxide. Science 1967; 158:1479–1480.

    Article  PubMed  CAS  Google Scholar 

  100. Hanig JP, Morrison JM, Krop S. Ethanol enhancement of blood-brain barrier permeability to catecholamines in chicks. Eur J Pharmacol 1972; 18:79–82.

    Article  PubMed  CAS  Google Scholar 

  101. Zhang YM, Liu N, Zhu ZH et al. Influence of different chelators (HYNIC, MAG3, and DTPA) on tumor cell accumulation and mouse biodistribution of technetium-99m labeled to antisense DNA. Eur J Nucl Med 2000; 27:1711–1707.

    Article  Google Scholar 

  102. Boado RJ, Pardridge WM. Ten nucleotide cis element in the 3′-untranslated region of the GLUT1 glucose transporter mRNA increases gene expression via mRNA stabilization. Mol Brain Res 1998; 59:109–113.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, UCLA, Los Angeles, California, USA

    Ruben J. Boado & William M. Pardridge

Authors
  1. Ruben J. Boado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William M. Pardridge
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Eurekah.com and Kluwer Academic / Plenum Publishers

About this chapter

Cite this chapter

Boado, R.J., Pardridge, W.M. (2006). Imaging Gene Expression in the Brain with Peptide Nucleic Acid (PNA) Antisense Radiopharmaceuticals and Drug Targeting Technology. In: Peptide Nucleic Acids, Morpholinos and Related Antisense Biomolecules. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-32956-0_4

Download citation

Publish with us

Policies and ethics

Search

Navigation