Oligonucleotides as Radiopharmaceuticals

  • B. Tavitian
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 49)

1.13 Conclusion

Oligonucleotide radiopharmaceuticals is a slowly but steadily progressing field. With a panel of labeling and imaging techniques mastered by several groups, imaging of oligonucleotides is now relatively accessible and will be applied to more and more trials of oligonucleotide pharmacology. Imaging with oligonucleotides is still a few miles farther ahead of us, but the stakes of detecting gene expression noninvasively in vivo are so high that it will certainly become a reality in the near future.


Antisense Oligonucleotide Peptide Nucleic Acid Cationic Lipid Curr Opin Chem Biol Antisense Drug 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agarwal N, Gewirtz AM (1999) Oligonucleotide therapeutics for hematologic disorders. Biochim Biophys Acta 1489:85–96PubMedGoogle Scholar
  2. Agrawal S (1996a) Antisense oligonucleotides: towards clinical trials. Trends Biotechnol 14:376–387PubMedCrossRefGoogle Scholar
  3. Agrawal S (1996b) Antisense therapeutics. Humana Press, TotawaCrossRefGoogle Scholar
  4. Akhtar S, Agrawal S (1997) In vivo studies with antisense oligonucleotides. Trends Pharmacol Sci 18:12–18PubMedCrossRefGoogle Scholar
  5. Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R, Iliakis G, Aiken RD (2001) Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulinlike growth factor type I receptor in malignant astrocytomas. J Clin Oncol 19:2189–2200PubMedGoogle Scholar
  6. Aurup H, Williams DM, Eckstein F (1992) 2′-Fluoro-and 2′-amino-2′-deoxynucleoside 5′-triphosphates as substrates for T7 RNA polymerase. Biochemistry 31:9636–9641PubMedCrossRefGoogle Scholar
  7. Azzazy HM, Hong K, Wu MC, Gross GW (1995) Interaction of cationic liposomes with cells of electrically active neuronal networks in culture. Brain Res 695:231–236PubMedCrossRefGoogle Scholar
  8. Benimetskaya L, Tonkinson JL, Koziolkiewicz M, Karwowski B, Guga P, Zeltser R, Stec W, Stein CA (1995) Binding of phosphorothioate oligodeoxynucleotides to basic fibroblast growth factor, recombinant soluble CD4, laminin and fibronectin is P-chirality independent. Nucleic Acids Res 23:4239–4245PubMedCrossRefGoogle Scholar
  9. Bianchini M, Radrizzani M, Brocardo MG, Reyes GB, Gonzalez Solveyra C, Santa-Coloma TA (2001) Specific oligobodies against ERK-2 that recognize both the native and the denatured state of the protein. J Immunol Methods 252:191–197PubMedCrossRefGoogle Scholar
  10. Bishop MR, Iversen PL, Bayever E, Sharp JG, I Greiner TC, Copple BL, Ruddon R, Zon G, Spinolo J, Arneson M, Armitage JO, Kessinger A (1996) Phase trial of an antisense oligonucleotide OL(1)p53 in hematologic malignancies. J Clin Oncol 14:1320–1326PubMedGoogle Scholar
  11. Blank M, Weinschenk T, Priemer M, Schluesener H (2001) Systematic evolution of a DNA aptamer binding to rat brain tumor microvessels selective targeting of endothelial regulatory protein pigpen. J Biol Chem 276: 16464–16468PubMedCrossRefGoogle Scholar
  12. Blasberg R (2002) PET imaging of gene expression. Eur J Cancer 38:2137–2146PubMedCrossRefGoogle Scholar
  13. Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci USA 92:7297–7301PubMedCrossRefGoogle Scholar
  14. Brody EN, Gold L (2000) Aptamers as therapeutic and diagnostic agents. J Biotechnol 74:5–13PubMedGoogle Scholar
  15. Caruthers MH, Beaucage SL, Efcavitch JW, Fisher EF, Matteucci MD, Stabinsky Y (1980) New chemical methods for synthesizing polynucleotides. Nucleic Acids Symp Ser 7:215–223PubMedGoogle Scholar
  16. Cerchia L, Hamm J, Libri D, Tavitian B, de Francis V (2002) Nucleic acid aptamers in cancer medicine. FEBS Lett 528:12–16PubMedCrossRefGoogle Scholar
  17. Charlton J, Sennello J, Smith D (1997) In vivo imaging of inflammation using an aptamer inhibitor of human neutrophil elastase. Chem Biol 4:809–816PubMedCrossRefGoogle Scholar
  18. Chow TY, Juby C, Brousseau R (1994) Specific targeting of antisense oligonucleotides to neutrophils. Antisense Res Dev 4:81–86PubMedGoogle Scholar
  19. Conrad R, Keranen LM, Ellington AD, Newton AC (1994) Isozyme-specific inhibition of protein kinase C by RNA aptamers. J Biol Chem 269: 32051–32054PubMedGoogle Scholar
  20. Cotter FE, Johnson P, Hall P, Pocock C, al Mahdi N, Cowell JK, Morgan G (1994) Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. Oncogene 9:3049–3055PubMedGoogle Scholar
  21. Crooke ST (1998) Antisense research and applications. Springer, Berlin Heidelberg New YorkGoogle Scholar
  22. Crooke ST (1999) Molecular mechanisms of action of antisense drugs. Biochim Biophys Acta 1489:31–44PubMedGoogle Scholar
  23. Crooke ST (2000) Evaluating the mechanism of action of antiproliferative antisense drugs. Antisense Nucleic Acid Drug Dev 10:123–127PubMedGoogle Scholar
  24. Dani C, Blanchard JM, Piechaczyk M, Riaad-El-Sabouty S, Marty L, Jeanteur P (1984) Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci USA 81:7046–7050PubMedCrossRefGoogle Scholar
  25. Dewanjee MK, Ghafouripour AK, Kapadvanjwala M, Dewanjee S, Serafini AN, Lopez DM, Sfakianakis GN (1994) Noninvasive imaging of c-myc oncogene messenger RNA with indium-111-antisense probes in a mammary tumor-bearing mouse model. J Nucl Med 35:1054–1063PubMedGoogle Scholar
  26. de Fabritiis P, Petti MC, Montefusco E, De Propris MS, Sala R, Bellucci R, Mancini M, Lisci A, Bonetto F, Geiser T, Calabretta B, Mandelli F (1998) BCR-ABL antisense oligodeoxynucleotide in vitro purging and autologous bone marrow transplantation for patients with chronic myelogenous leukemia in advanced phase. Blood 91:3156–3162PubMedGoogle Scholar
  27. Dollé F, Hinnen F, Vaufrey F, Tavitian B, Crouzel C (1997) A general method for labeling oligodeoxynucleotides with 18F for in vivo PET imaging. J Label Compounds Radiopharm 34:319–330CrossRefGoogle Scholar
  28. Doudna JA, Cech TR, Sullenger BA (1995) Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor. Proc Natl Acad Sci USA 92:2355–2359PubMedCrossRefGoogle Scholar
  29. Dougan H, Weitz JI, Stafford AR, Gillespie KD, Klement P, Hobbs JB, Lyster DM (2003) Evaluation of DNA aptamers directed to thrombin as potential thrombus imaging agents. Nucl Med Biol 30:61–72PubMedCrossRefGoogle Scholar
  30. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822PubMedCrossRefGoogle Scholar
  31. Famulok M, Jenne A (1998) Oligonucleotide libraries-variation delectat. Curr Opin Chem Biol 2:320–327PubMedCrossRefGoogle Scholar
  32. Famulok M, Mayer G, Blind M (2000) Nucleic acid aptamers — from selection in vitro to applications in vivo. Acc Chem Res 33:591–599PubMedCrossRefGoogle Scholar
  33. Faria M, Spiller DG, Dubertret C, Nelson JS, White MR, Scherman D, Helene C, Giovannangeli C (2001) Phosphoramidate oligonucleotides as potent antisense molecules in cells and in vivo. Nat Biotechnol 19:40–44PubMedCrossRefGoogle Scholar
  34. Feigner PL, Barenholz Y, Behr JP, Cheng SH, Cullis P, Huang L, Jessee JA, Seymour L, Szoka F, Thierry AR, Wagner E, Wu G (1997) Nomenclature for synthetic gene delivery systems. Hum Gene Ther 8:511–512CrossRefGoogle Scholar
  35. Freier S (1993) Hybridization: considerations affecting antisense drugs. In: Crooke ST, Lebleu B (eds) Antisense research and applications. CRC Press, Boca Raton, pp 67–82Google Scholar
  36. Geromel V, Cao A, Briane D, Vassy J, Rotig A, Rustin P, Coudert R, Rigaut JP, Munnich A, Taillandier E (2001) Mitochondria transfection by oligonucleotides containing a signal peptide and vectorized by cationic liposomes. Antisense Nucleic Acid Drug Dev 11:175–180PubMedCrossRefGoogle Scholar
  37. Geselowitz DA, Neckers LM (1992) Analysis of oligonucleotide binding, internalization, and intracellular trafficking utilizing a novel radiolabeled crosslinker. Antisense Res Dev 2:17–25PubMedGoogle Scholar
  38. Geselowitz DA, Neckers LM (1995) Bovine serum albumin is a major oligonucleotide-binding protein found on the surface of cultured cells. Antisense Res Dev 5:213–217PubMedGoogle Scholar
  39. Gold L (1995) Oligonucleotides as research, diagnostic, and therapeutic agents. J Biol Chem 270:13581–13584PubMedGoogle Scholar
  40. Hamzavi R, Dollé F, Tavitian B, Dahl O, Nielsen P (2003) Modulation of the pharmacokinetic properties of PNA: preparation of galactosyl, mannosyl, fucosyl, N-acetyl-galatosaminyl and N-acetyl-glycosaminyl derivatives of aminoethylglycin peptide nucleic acid monomers and their incorporation into PNA oligomers. Bioconj Chem 14:941–954CrossRefGoogle Scholar
  41. Hawley P, Gibson I (1996) Interaction of oligodeoxynucleotides with mammalian cells. Antisense Nucleic Acid Drug Dev 6:185–195PubMedGoogle Scholar
  42. Henry SP, Novotny W, Leeds J, Auletta C, Kornbrust DJ (1997) Inhibition of coagulation by a phosphorothioate oligonucleotide. Antisense Nucleic Acid Drug Dev 7:503–510PubMedGoogle Scholar
  43. Hermann T, Patel DJ (2000) Adaptive recognition by nucleic acid aptamers. Science 287:820–825PubMedCrossRefGoogle Scholar
  44. Hicke BJ, Marion C, Chang YF, Gould T, Lynott CK, Parma D, Schmidt PG, Warren S (2001) Tenascin-C aptamers are generated using tumor cells and purified protein. J Biol Chem 276:48644–48654PubMedCrossRefGoogle Scholar
  45. Hjelstuen OK, Tonnesen HH, Bremer PO, Verbruggen AM (1998) 3′-99mTc-labeling and biodistribution of a CAPL antisense oligodeoxynucleotide. Nucl Med Biol 25:651–657PubMedCrossRefGoogle Scholar
  46. Hnatowich DJ, Mardirossian G, Fogarasi M, Sano T, Smith CL, Cantor CR, Rusckowski M, Winnard PJ (1996) Comparative properties of a technetium-99m-labeled single-stranded natural DNA and a phosphorothioate derivative in vitro and in mice. J Pharm Exp Ther 276:326–334Google Scholar
  47. Hnatowich DJ (1999) Changing focus: applying antisense to nuclear medicine imaging. Mol Med Today 5:151PubMedCrossRefGoogle Scholar
  48. Hogrefe RI (1999) An antisense oligonucleotide primer. Antisense Nucleic Acid Drug Dev 9:351–357PubMedGoogle Scholar
  49. Jacobs A, Voges J, Reszka R, Lercher M, Gossmann A, Kracht L, Kaestle C, Wagner R, Wienhard K, Heiss WD (2001) Positronemission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 358:727–729PubMedCrossRefGoogle Scholar
  50. Jain RK (1998) The next frontier of molecular medicine: delivery of therapeutics. Nat Med 4:655–657PubMedCrossRefGoogle Scholar
  51. Jansen B, Schlagbauer-Wadl H, Brown BD, Bryan RN, van Elsas A, Muller M, Wolff K, Eichler HG, Pehamberger H (1998) bcl-2 antisense therapy chemosensitizes human melanoma in SCID mice. Nat Med 4:232–234PubMedCrossRefGoogle Scholar
  52. Jansen B, Wacheck V, Heere-Ress E, Schlagbauer-Wadl H, Hoeller C, Lucas T, Hoermann M, Hollenstein U, Wolff K, Pehamberger H (2000) Chemosensitization of malignant melanoma by BCL2 antisense therapy. Lancet 356:1728–1733PubMedCrossRefGoogle Scholar
  53. Jayasena SD (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin Chem 45:1628–1650PubMedGoogle Scholar
  54. Jhaveri S, Rajendran M, Ellington AD (2000) In vitro selection of signaling aptamers. Nat Biotechnol 18:1293–1297PubMedCrossRefGoogle Scholar
  55. Kaesh S, Kim JB, Cariola M, Ralston E (1996) Improved lipid-mediated gene transfer into primary cultures of hippocampal neurons. Mol Brain Res 35:344–348CrossRefGoogle Scholar
  56. Kedzierski W, Porter JC (1990) Quantitative study of tyrosine hydroxylase mRNA in catecholaminergic neurons and adrenals during development and aging. Mol Brain Res 7:45–51PubMedCrossRefGoogle Scholar
  57. Kimoto M, Shirouzu M, Mizutani S, Koide H, Kaziro Y, Hirao I, Yokoyama S (2002) Anti-(Raf-1) RNA aptamers that inhibit Ras-induced Raf-1 activation. Eur J Biochem 269:697–704PubMedCrossRefGoogle Scholar
  58. Kobori N, Imahori Y, Mineura K, Ueda S, Fujii R (1999) Visualization of mRNA expression in CNS using nC-labeled phosphorothioate oligodeoxynucleotide. Neuroreport 10:2971–2974PubMedCrossRefGoogle Scholar
  59. Krieg AM (2001) From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA. Antisense Nucleic Acid Drug Dev 11:181–188PubMedCrossRefGoogle Scholar
  60. Kühnast B, Dollé F, Tavitian B (2002) Fluorine-18 labeling of peptide nucleic acids. J Label Compounds Radiopharm 45:1–11CrossRefGoogle Scholar
  61. Kühnast B, Dollé F, Vaufrey F, Hinnen F, Crouzel C, Tavitian B (2000 a) Fluorine-18 labeling of oligonucleotides bearing chemically-modified ribose-phosphate backbones. J Label Compounds Radiopharm 43:837–848CrossRefGoogle Scholar
  62. Kühnast B, Dollé F, Terrazzino S, Rousseau B, Loc’h C, Vaufrey F, Hinnen F, Doignon I, Pillon F, David C, Crouzel C, Tavitian B (2000 b) A general method to label antisense oligonucleotides with radioactive halogens for pharmacological and imaging studies. Bioconj Chem 11:627–636CrossRefGoogle Scholar
  63. Kuhnast B, Hinnen F, Boisgard R, Tavitian B, Dollé F (2003b) Fluorine-18 labeling of oligonucleotides: prosthetic labeling at the 5′-end using theN-(4-[18F]fluorobenzyl)-2-bromoacetamide reagent. J Label Compounds Radiopharm 46:1093–1103CrossRefGoogle Scholar
  64. Kühnast B, Klussmann S, Hinnen F, Boisgard R, Rousseau B, Fürste JP, Tavitian B, Dollé F (2003 a) Fluorine-18-and iodine-125 labeling of Spiegelmers. J Label Compounds Radiopharm 46:1205–1219CrossRefGoogle Scholar
  65. Lambert G, Fattal E, Couvreur P (2001) Nanoparticulate systems for the delivery of antisense oligonucleotides. Adv Drug Deliv Rev 47:99–112PubMedCrossRefGoogle Scholar
  66. Lavigne C, Thierry AR (1997) Enhanced antisense inhibition of human immunodeficiency virus type 1 in cell cultures by DLS delivery system. Biochem Biophys Res Commun 237:566–571PubMedCrossRefGoogle Scholar
  67. Lavorgna G, Dahary D, Lehner B, Sorek R, Sanderson CM, Casari G (2004) In search of antisense. Trends Biochem Sci 29:88–94PubMedCrossRefGoogle Scholar
  68. Lewis MR, Jia F (2003) Antisense imaging: and miles to go before we sleep? J Cell Biochem 90:464–472PubMedCrossRefGoogle Scholar
  69. Ma DD, Wei AQ (1996) Enhanced delivery of synthetic oligonucleotides to human leukaemic cells by liposomes and immunoliposomes. Leuk Res 20:925–930PubMedCrossRefGoogle Scholar
  70. Mardirossian G, Lei K, Rusckowski M, Chang F, Qu T, Egholm M, Hnato-wich DJ (1997) In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA). J Nucl Med 38:907–913PubMedGoogle Scholar
  71. Maus U, Rosseau S, Mandrakas N, Schlingensiepen R, Maus R, Muth H, Grimminger F, Seeger W, Lohmeyer J (1999) Cationic lipids employed for antisense oligodeoxynucleotide transport may inhibit vascular cell adhesion molecule-1 expression in human endothelial cells: a word of caution. Antisense Nucleic Acid Drug Dev 9:71–80PubMedGoogle Scholar
  72. Miyashita T, Reed JC (1993) Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 81:151–157PubMedGoogle Scholar
  73. Monia BP, Johnston JF, Ecker DJ, Zounes MA, Lima WF, Freier SM (1992) Selective inhibition of mutant Ha-ras mRNA expression by antisense oligonucleotides. J Biol Chem 267:19954–19962PubMedGoogle Scholar
  74. Morris KN, Jensen KB, Julin CM, Weil M, Gold L (1998) High affinity ligands from in vitro selection: complex targets. Proc Natl Acad Sci USA 95:2902–2907PubMedCrossRefGoogle Scholar
  75. Osborne SE, Ellington AD (1997) Nucleic acid selection and the challenge of combinatorial chemistry. Chem Rev 97:349–370PubMedCrossRefGoogle Scholar
  76. Osborne SE, Matsumura I, Ellington AD (1997) Aptamers as therapeutic and diagnostic reagents: problems and prospects. Curr Opin Chem Biol 1:5–9PubMedCrossRefGoogle Scholar
  77. Ostendorf T, Kunter U, Grone HJ, Bahlmann F, Kawachi H, Shimizu F, Koch KM, Janjic N, Floege J (2001) Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis. J Am Soc Nephrol 12:909–918PubMedGoogle Scholar
  78. Pardridge WM (1997) Drug delivery to the brain. J Cereb Blood Flow Metab 17:713–731PubMedCrossRefGoogle Scholar
  79. Pietras K, Ostman A, Sjoquist M, Buchdunger E, Reed RK, Heldin CH, Rubin K (2001) Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Cancer Res 61:2929–2934PubMedGoogle Scholar
  80. Piwnica Worms D (1994) Making sense out of anti-sense: challenges of imaging gene translation with radiolabeled oligonucleotides. J Nucl Med 35:1064–1066PubMedGoogle Scholar
  81. Prochiantz A (1998) Peptide nucleic acid smugglers. Nat Biotechnol 16: 819–820PubMedCrossRefGoogle Scholar
  82. Ratajczak MZ, Kant JA, Luger SM, Hijiya N, Zhang J, Zon G, Gewirtz AM (1992) In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides. Proc Natl Acad Sci USA 89: 11823–11827PubMedCrossRefGoogle Scholar
  83. Roivainen A, Tolvanen T, Salomaki S, Lendvai G, Velikyan I, Numminen P, Valila M, Sipila H, Bergstrom M, Harkonen P, Lonnberg H, Langstrom B (2004) 68 Ga-labeled oligonucleotides for in vivo imaging with PET. J Nucl Med 45:347–355PubMedGoogle Scholar
  84. Ruckman J, Green LS, Beeson J, Waugh S, Gillette WL, Henninger DD, Claesson-Welsh L, Janjic N (1998) 2’-Fluoropyrimidine RNA-based apta-mers to the 165-amino acid form of vascular endothelial growth factor (VEGF165). Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain. J Biol Chem 273:20556–20567PubMedCrossRefGoogle Scholar
  85. Rusckowski M, Qu T, Chang F, Hnatowich DJ (1997) Pretargeting using peptide nucleic acid. Cancer 80:2699–2705PubMedCrossRefGoogle Scholar
  86. Sauer M, Brecht A, Charisse K, Maier M, Gerster M, Stemmler I, Gauglitz G, Bayer E (1999) Interaction of chemically modified antisense oligonucleotides with sense DNA: a label-free interaction study with reflecto-metric interference spectroscopy. Anal Chem 71:2850–2857PubMedCrossRefGoogle Scholar
  87. Schwab G, Chavany C, Duroux I, Goubin G, Lebeau J, Helene C, Saison Behmoaras T (1994) Antisense oligonucleotides adsorbed to polyalkyl-cyanoacrylate nanoparticles specifically inhibit mutated Haras-mediated cell proliferation and tumorigenicity in nude mice. Proc Natl Acad Sci USA 91:10460–10464PubMedCrossRefGoogle Scholar
  88. Sethi S, Lipford G, Wagner H, Kretzschmar H (2002) Postexposure prophylaxis against prion disease with a stimulator of innate immunity. Lancet 360:229–230PubMedCrossRefGoogle Scholar
  89. Shi N, Boado RJ, Pardridge RW (2000) Antisense imaging of gene expression in the brain in vivo. Proc Natl Acad Sci USA 97:14709–14714PubMedCrossRefGoogle Scholar
  90. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 598:503–517CrossRefGoogle Scholar
  91. Srinivasan SK, Tewary HK, Iversen PL (1995) Characterization of binding sites, extent of binding, and drug interactions of oligonucleotides with albumin. Antisense Res Dev 5:131–139PubMedGoogle Scholar
  92. Stein CA (1999) Keeping the biotechnology of antisense in context. Nat Biotech 17:209CrossRefGoogle Scholar
  93. Sun S (2000) Technology evaluation: SELEX, Gilead Sciences Inc. Curr Opin Mol Ther 2:100–105PubMedGoogle Scholar
  94. Sussman D, Nix JC, Wilson C (2000) The structural basis for molecular recognition by the vitamin B 12 RNA aptamer. Nat Struct Biol 7:53–57PubMedCrossRefGoogle Scholar
  95. Tavitian B, Marzabal S, Boutet V, Kühnast B, Terrazzino S, Moynier M, Dollé F, Deverre JR, Thierry AR (2002) Characterization of a synthetic anionic vector for oligonucleotide delivery using in vivo whole body dynamic imaging. Pharm Res 19:367–376PubMedCrossRefGoogle Scholar
  96. Tavitian B, Terrazzino S, Kühnast B, Marzabal S, Stettler O, Dollé F, Deverre JR, Jobert A, Hinnen F, Bendriem B, Crouzel C, Di Giamberardino L (1998) In vivo imaging of oligonucleotides with positron emission tomography. Nat Med 4:467–471PubMedCrossRefGoogle Scholar
  97. Tavitian B (2000) In vivo antisense imaging. Q J Nucl Med 44:236–255PubMedGoogle Scholar
  98. Thierry AR, Dritschilo A (1992) Intracellular availability of unmodified, phosphorothioated and liposomally encapsulated oligodeoxynucleotides for antisense activity. Nucleic Acids Res 20:5691–5698PubMedCrossRefGoogle Scholar
  99. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510PubMedCrossRefGoogle Scholar
  100. Urbain JL (2001) Sense, antisense, and common sense. J Nucl Med 42: 1670–1672PubMedGoogle Scholar
  101. Usman N, Blatt LM (2000) Nuclease-resistant synthetic ribozymes: developing a new class of therapeutics. J Clin Invest 106:1197–1202PubMedCrossRefGoogle Scholar
  102. Wang S, Lee RJ, Cauchon G, Gorenstein DG, Low PS (1995) Delivery of antisense oligodeoxyribonucleotides against the human epidermal growth factor receptor into cultured KB cells with liposomes conjugated to folate via polyethylene glycol. Proc Natl Acad Sci USA 92:3318–3322PubMedCrossRefGoogle Scholar
  103. Wang Y, Chang F, Zhang Y, Liu N, Liu G, Gupta S, Rusckowski M, Hnato-wich DJ (2001) Pretargeting with amplification using polymeric peptide nucleic acid. Bioconjug Chem 12:807–816PubMedCrossRefGoogle Scholar
  104. White RR, Sullenger BA, Rusconi CP (2000) Developing aptamers into therapeutics. J Clin Invest 106:929–934PubMedCrossRefGoogle Scholar
  105. Wickstrom E (1998) Clinical trials of genetic therapy with antisense DNA and DNA vectors. Marcel Decker, New YorkGoogle Scholar
  106. Willis MC, Collins BD, Zhang T, Green LS, Sebesta DP, Bell C, Kellogg E, Gill SC, Magallanez A, Knauer S, Bendele RA, Gill PS, Janjic N, Collins B (1998) Liposome-anchored vascular endothelial growth factor aptamers. Bioconjug Chem 9:573–582PubMedCrossRefGoogle Scholar
  107. Wilson DS, Szostak JW (1999) In vitro selection of functional nucleic acids. Annu Rev Biochem 68:611–647PubMedCrossRefGoogle Scholar
  108. Wlotzka B, Leva S, Eschgfaller B, Burmeister J, Kleinjung F, Kaduk C, Muhn P, Hess-Stumpp H, Klussmann S (2002) In vivo properties of an anti-GnRH Spiegelmer: an example of an oligonucleotide-based therapeutic substance class. Proc Natl Acad Sci USA 99:8898–8902PubMedCrossRefGoogle Scholar
  109. Woolf TM, Melton DA, Jennings CG (1992) Specificity of antisense oligo-nucleotides in vivo. Proc Natl Acad Sci USA 89:7305–7309PubMedCrossRefGoogle Scholar
  110. Wu F, Yngve U, Hedberg E, Honda M, Lu L, Eriksson B, Watanabe Y, Bergstrom M, Langstrom B (2000) Distribution of [76Br]-labeled anti-sense oligonucleotides of different length determined ex vivo in rats. Eur J Pharm Sci 10:179–186PubMedCrossRefGoogle Scholar
  111. Yakubov LA, Deeva EA, Zarytova VF, Ivanova EM, Ryte AS, Yurchenko LV, Vlassov VV (1989) Mechanism of oligonucleotide uptake by cells: involvement of specific receptors? Proc Natl Acad Sci USA 86:6454–6458PubMedCrossRefGoogle Scholar
  112. Younes CK, Boisgard R, Tavitian B (2002) Labeled oligonucleotides as radio-pharmaceuticals: pitfalls, problems and perspectives. Curr Pharm Des 8: 1451–1466PubMedCrossRefGoogle Scholar
  113. Zamecnik PC, Stephenson ML (1978) Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc Natl Acad Sci USA 75:280–284PubMedCrossRefGoogle Scholar
  114. Zelphati O, Szoka FC Jr (1996) Mechanism of oligonucleotide release from cationic liposomes. Proc Natl Acad Sci USA 93:11493–11498PubMedCrossRefGoogle Scholar
  115. Zhang YM, Liu N, Zhu ZH, Rusckowski M, Hnatowich DJ (2000) 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 27:1700–1707PubMedCrossRefGoogle Scholar
  116. Zhang YM, Wang Y, Liu N, Zhu ZH, Rusckowski M, Hnatowich DJ (2001) In vitro investigations of tumor targeting with [99m]Tc-labeled antisense DNA. J Nucl Med 42:1660–1669PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • B. Tavitian
    • 1
  1. 1.Frédéric Joliot CEA Direction des Sciences du Vivant Direction de la Recherche MedicaleINSERM ERM 103 Service HospitalierOrsay CedexFrance

Personalised recommendations