Auger radiation targeted into DNA: a therapy perspective

  • Franz Buchegger
  • Florence Perillo-Adamer
  • Yves M. Dupertuis
  • Angelika Bischof Delaloye
Review article



Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of α particles. In contrast to α radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies.


Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided α and β radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation.


Auger radiation Nuclear targeting Treatment Dosimetry 


  1. 1.
    Larson SM, Krenning EP. A pragmatic perspective on molecular targeted radionuclide therapy. J Nucl Med 2005;46 Suppl 1:1S–3SPubMedGoogle Scholar
  2. 2.
    Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med 1998;338:297–306PubMedGoogle Scholar
  3. 3.
    Feinendegen LE. Contributions of nuclear medicine to the therapy of malignant tumors. J Cancer Res Clin Oncol 1993;119:320–322PubMedGoogle Scholar
  4. 4.
    Boelaert K, Franklyn JA. Sodium iodide symporter: a novel strategy to target breast, prostate, and other cancers? Lancet 2003;361:796–797PubMedGoogle Scholar
  5. 5.
    Berlin NI, Wasserman LR. Polycythemia vera: a retrospective and reprise. J Lab Clin Med 1997;130:365–373PubMedGoogle Scholar
  6. 6.
    Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol 2005;6:392–400PubMedGoogle Scholar
  7. 7.
    Liepe K, Runge R, Kotzerke J. Systemic radionuclide therapy in pain palliation. Am J Hosp Palliat Care 2005;22:457–464PubMedGoogle Scholar
  8. 8.
    Bauman G, Charette M, Reid R, Sathya J. Radiopharmaceuticals for the palliation of painful bone metastasis—a systemic review. Radiother Oncol 2005;75:258–270PubMedGoogle Scholar
  9. 9.
    Mach JP, Carrel S, Merenda C, Sordat B, Cerottini JC. In vivo localisation of radiolabelled antibodies to carcinoembryonic antigen in human colon carcinoma grafted into nude mice. Nature 1974;248:704–706PubMedGoogle Scholar
  10. 10.
    Primus FJ, Wang RH, Goldenberg DM, Hansen HJ. Localization of human GW-39 tumors in hamsters by radiolabeled heterospecific antibody to carcinoembryonic antigen. Cancer Res 1973;33:2977–2982PubMedGoogle Scholar
  11. 11.
    Goldenberg DM. Advancing role of radiolabeled antibodies in the therapy of cancer. Cancer Immunol Immunother 2003;52:281–296PubMedGoogle Scholar
  12. 12.
    Juweid ME. Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma: from clinical trials to clinical practice. J Nucl Med 2002;43:1507–1529PubMedGoogle Scholar
  13. 13.
    Otte A, Jermann E, Behe M, Goetze M, Bucher HC, Roser HW, et al. DOTATOC: a powerful new tool for receptor–mediated radionuclide therapy. Eur J Nucl Med 1997;24:792–795PubMedGoogle Scholar
  14. 14.
    Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet 1998;351:417–418PubMedGoogle Scholar
  15. 15.
    Couturier O, Supiot S, Graef-Mougin M, Faivre-Chauvet A, Carlier T, Chatal JF, et al. Cancer radioimmunotherapy with alpha-emitting nuclides. Eur J Nucl Med Mol Imaging 2005;32:601–614PubMedGoogle Scholar
  16. 16.
    Mulford DA, Scheinberg DA, Jurcic JG. The promise of targeted {alpha}-particle therapy. J Nucl Med 2005;46 Suppl 1:199S–204SPubMedGoogle Scholar
  17. 17.
    Thames HD, Hendry JH. Fractionation in radiotherapy. 1st edn. London: Taylor and Francis, 1987Google Scholar
  18. 18.
    DeNardo GL, Schlom J, Buchsbaum DJ, Meredith RF, O’Donoghue JA, Sgouros G, et al. Rationales, evidence, and design considerations for fractionated radioimmunotherapy. Cancer 2002;94:1332–1348PubMedGoogle Scholar
  19. 19.
    Kassis AI, Adelstein SJ. Radiobiologic principles in radionuclide therapy. J Nucl Med 2005;46:4S–12SPubMedGoogle Scholar
  20. 20.
    Valerie K, Povirk LF. Regulation and mechanisms of mammalian double-strand break repair. Oncogene 2003;22:5792–5812PubMedGoogle Scholar
  21. 21.
    Vilenchik MM, Knudson AG. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci USA 2003;100:12871–12876PubMedGoogle Scholar
  22. 22.
    De Jong M, Kwekkeboom D, Valkema R, Krenning EP. Radiolabelled peptides for tumour therapy: current status and future directions. Plenary lecture at the EANM 2002. Eur J Nucl Med Mol Imaging 2003;30:463–469PubMedCrossRefGoogle Scholar
  23. 23.
    Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, et al. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin’s lymphomas. J Clin Oncol 2005;23:7565–7573PubMedGoogle Scholar
  24. 24.
    Gordon LI, Molina A, Witzig T, Emmanouilides C, Raubitschek A, Darif M, et al. Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase I/II study. Blood 2004;103:4429–4431PubMedGoogle Scholar
  25. 25.
    Press OW, Rasey J. Principles of radioimmunotherapy for hematologists and oncologists. Semin Oncol 2000;27:62–73PubMedGoogle Scholar
  26. 26.
    Faderl S, Coutre S, Byrd JC, Dearden C, Denes A, Dyer MJ, et al. The evolving role of alemtuzumab in management of patients with CLL. Leukemia 2005;19:2147–2152PubMedGoogle Scholar
  27. 27.
    McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;16:2825–2833PubMedGoogle Scholar
  28. 28.
    Neyt M, Albrecht J, Cocquyt V. An economic evaluation of Herceptin in adjuvant setting: the Breast Cancer International Research Group 006 trial. Ann Oncol 2006;17:381–390PubMedGoogle Scholar
  29. 29.
    Trümper L. Radioimmuntherapie in der Hämatologie und Onkologie. 1st edn. Bremen: Uni-Med Science, 2005Google Scholar
  30. 30.
    O’Donoghue JA, Bardies M, Wheldon TE. Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med 1995;36:1902–1909PubMedGoogle Scholar
  31. 31.
    Vogel CA, Galmiche MC, Buchegger F. Radioimmunotherapy and fractionated radiotherapy of human colon cancer liver metastases in nude mice. Cancer Res 1997;57:447–453PubMedGoogle Scholar
  32. 32.
    Sharkey RM, Weadock KS, Natale A, Haywood L, Aninipot R, Blumenthal RD, et al. Successful radioimmunotherapy for lung metastasis of human colonic cancer in nude mice. J Natl Cancer Inst 1991;83:627–632PubMedGoogle Scholar
  33. 33.
    Hindorf C, Emfietzoglou D, Linden O, Kostarelos K, Strand SE. Internal microdosimetry for single cells in radioimmunotherapy of B-cell lymphoma. Cancer Biother Radiopharm 2005;20:224–230PubMedGoogle Scholar
  34. 34.
    De Jong M, Breeman WA, Valkema R, Bernard BF, Krenning EP. Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs. J Nucl Med 2005;46 Suppl 1:13S–17SPubMedGoogle Scholar
  35. 35.
    Auger P. Sur les rayons beta secondaires produits dans un gaz par des rayons X. Comp Rend 1925;180:65–68Google Scholar
  36. 36.
    O’Donoghue JA, Wheldon TE. Targeted radiotherapy using Auger electron emitters. Phys Med Biol 1996;41:1973–1992PubMedGoogle Scholar
  37. 37.
    Sastry KS. Biological effects of the Auger emitter iodine-125: a review. Report No. 1 of AAPM Nuclear Medicine Task Group No. 6. Med Phys 1992;19:1361–1370PubMedGoogle Scholar
  38. 38.
    Howell RW. Radiation spectra for Auger-electron emitting radionuclides: report No. 2 of AAPM Nuclear Medicine Task Group No. 6. Med Phys 1992;19:1371–1383PubMedGoogle Scholar
  39. 39.
    Humm JL, Howell RW, Rao DV. Dosimetry of Auger-electron-emitting radionuclides: report no. 3 of AAPM Nuclear Medicine Task Group No. 6. Med Phys 1994;21:1901–1915PubMedGoogle Scholar
  40. 40.
    Kassis AI, Fayad F, Kinsey BM, Sastry KS, Taube RA, Adelstein SJ. Radiotoxicity of 125I in mammalian cells. Radiat Res 1987;111:305–318PubMedGoogle Scholar
  41. 41.
    Howell RW, Narra VR, Sastry KS, Rao DV. On the equivalent dose for Auger electron emitters. Radiat Res 1993;134:71–78PubMedGoogle Scholar
  42. 42.
    Lobachevsky PN, Martin RF. Iodine-125 decay in a synthetic oligodeoxynucleotide. I. Fragment size distribution and evaluation of breakage probability. Radiat Res 2000;153:263–270PubMedGoogle Scholar
  43. 43.
    Lobachevsky PN, Karagiannis TC, Martin RF. Plasmid DNA breakage by decay of DNA-associated Auger electron emitters: approaches to analysis of experimental data. Radiat Res 2004;162:84–95PubMedGoogle Scholar
  44. 44.
    Panyutin IG, Neumann RD. The potential for gene-targeted radiation therapy of cancers. Trends Biotechnol 2005;23:492–496PubMedGoogle Scholar
  45. 45.
    Bishayee A, Rao DV, Howell RW. Radiation protection by cysteamine against the lethal effects of intracellularly localized Auger electron, alpha- and beta-particle emitting radionuclides. Acta Oncol 2000;39:713–720PubMedGoogle Scholar
  46. 46.
    Bishayee A, Hill HZ, Stein D, Rao DV, Howell RW. Free radical-initiated and gap junction-mediated bystander effect due to nonuniform distribution of incorporated radioactivity in a three-dimensional tissue culture model. Radiat Res 2001;155:335–344PubMedGoogle Scholar
  47. 47.
    Makrigiorgos GM, Kassis AI, Baranowska-Kortylewicz J, McElvany KD, Welch MJ, Sastry KS, et al. Radiotoxicity of 5-[123I]iodo-2′-deoxyuridine in V79 cells: a comparison with 5-[125I]iodo-2′-deoxyuridine. Radiat Res 1989;118:532–544PubMedGoogle Scholar
  48. 48.
    Rao DV, Narra VR, Howell RW, Govelitz GF, Sastry KS. In-vivo radiotoxicity of DNA-incorporated 125I compared with that of densely ionising alpha-particles. Lancet 1989;2:650–653PubMedGoogle Scholar
  49. 49.
    Pomplun E, Booz J, Dydejczyk A, Feinendegen LE. A microdosimetric interpretation of the radiobiological effectiveness of 125I and the problem of quality factor. Radiat Environ Biophys 1987;26:181–188PubMedGoogle Scholar
  50. 50.
    Howell RW, Rao DV, Hou DY, Narra VR, Sastry KS. The question of relative biological effectiveness and quality factor for Auger emitters incorporated into proliferating mammalian cells. Radiat Res 1991;128:282–292PubMedGoogle Scholar
  51. 51.
    Narra VR, Howell RW, Harapanhalli RS, Sastry KS, Rao DV. Radiotoxicity of some iodine-123, iodine-125 and iodine-131-labeled compounds in mouse testes: implications for radiopharmaceutical design. J Nucl Med 1992;33:2196–2201PubMedGoogle Scholar
  52. 52.
    Hoyes KP, Nettleton JS, Lawson RS, Morris ID. Transferrin-dependent uptake and dosimetry of Auger-emitting diagnostic radionuclides in human spermatozoa. J Nucl Med 1998;39:895–899PubMedGoogle Scholar
  53. 53.
    Hoyes KP, Morris ID, Hendry JH, Sharma HL. Transferrin-mediated uptake of radionuclides by the testis. J Nucl Med 1996;37:336–340PubMedGoogle Scholar
  54. 54.
    Hoyes KP, Johnson C, Johnston RE, Lendon RG, Hendry JH, Sharma HL, et al. Testicular toxicity of the transferrin binding radionuclide 114mIn in adult and neonatal rats. Reprod Toxicol 1995;9:297–305PubMedGoogle Scholar
  55. 55.
    Hoyes KP, Lord BI, McCann C, Hendry JH, Morris ID. Transgenerational effects of preconception paternal contamination with (55)Fe. Radiat Res 2001;156:488–494PubMedGoogle Scholar
  56. 56.
    Blasberg RG, Roelcke U, Weinreich R, Beattie B, von Ammon K, Yonekawa Y, et al. Imaging brain tumor proliferative activity with [124I]iododeoxyuridine. Cancer Res 2000;60:624–635PubMedGoogle Scholar
  57. 57.
    Xue LY, Butler NJ, Makrigiorgos GM, Adelstein SJ, Kassis AI. Bystander effect produced by radiolabeled tumor cells in vivo. Proc Natl Acad Sci USA 2002;99:13765–13770PubMedGoogle Scholar
  58. 58.
    Sgouros G. Dosimetry of internal emitters. J Nucl Med 2005;46 Suppl 1:18S–27SPubMedGoogle Scholar
  59. 59.
    Stabin MG, Howell RW, Colas-Linhart NC. Modeling radiation dose and effects from internal emitters in nuclear medicine: from the whole body to individual cells. Cell Mol Biol (Noisy-le-grand) 2001;47:535–543Google Scholar
  60. 60.
    Goddu SM, Howell RW, Rao DV. Calculation of equivalent dose for Auger electron emitting radionuclides distributed in human organs. Acta Oncol 1996;35:909–916PubMedGoogle Scholar
  61. 61.
    Buchegger F, Vieira JM, Blaeuenstein P, Dupertuis YM, Schaffland AO, Grannavel C, et al. Preclinical Auger and gamma radiation dosimetry for fluorodeoxyuridine-enhanced tumour proliferation scintigraphy with [123I]iododeoxyuridine. Eur J Nucl Med Mol Imaging 2003;30:239–246PubMedCrossRefGoogle Scholar
  62. 62.
    Kassis AI, Sastry KS, Adelstein SJ. Kinetics of uptake, retention, and radiotoxicity of 125IUdR in mammalian cells: implications of localized energy deposition by Auger processes. Radiat Res 1987;109:78–89PubMedGoogle Scholar
  63. 63.
    Di Croce L, Okret S, Kersten S, Gustafsson JA, Parker M, Wahli W, et al. Steroid and nuclear receptors. Villefranche-sur-Mer, France, May 25–27, 1999. EMBO J 1999;18:6201–6210PubMedGoogle Scholar
  64. 64.
    Beato M, Truss M, Chavez S. Control of transcription by steroid hormones. Ann N Y Acad Sci 1996;784:93–123PubMedGoogle Scholar
  65. 65.
    Yasui LS, Hughes A, DeSombre ER. Cytotoxicity of 125I-oestrogen decay in non-oestrogen receptor-expressing human breast cancer cells, MDA-231 and oestrogen receptor-expressing MCF-7 cells. Int J Radiat Biol 2001;77:955–962PubMedGoogle Scholar
  66. 66.
    Yasui L, Hughes A, DeSombre E. Relative biological effectiveness of accumulated 125IdU and 125I-estrogen decays in estrogen receptor-expressing MCF-7 human breast cancer cells. Radiat Res 2001;155:328–334PubMedGoogle Scholar
  67. 67.
    DeSombre ER, Hughes A, Hanson RN, Kearney T. Therapy of estrogen receptor-positive micrometastases in the peritoneal cavity with Auger electron-emitting estrogens—theoretical and practical considerations. Acta Oncol 2000;39:659–666PubMedGoogle Scholar
  68. 68.
    Reilly RM, Kiarash R, Cameron RG, Porlier N, Sandhu J, Hill RP, et al. 111In-labeled EGF is selectively radiotoxic to human breast cancer cells overexpressing EGFR. J Nucl Med 2000;41:429–438PubMedGoogle Scholar
  69. 69.
    Chen P, Cameron R, Wang J, Vallis KA, Reilly RM. Antitumor effects and normal tissue toxicity of 111In-labeled epidermal growth factor administered to athymic mice bearing epidermal growth factor receptor-positive human breast cancer xenografts. J Nucl Med 2003;44:1469–1478PubMedGoogle Scholar
  70. 70.
    Andersson P, Forssell-Aronsson E, Johanson V, Wangberg B, Nilsson O, Fjalling M, et al. Internalization of indium-111 into human neuroendocrine tumor cells after incubation with indium-111-DTPA-D-Phe1-octreotide. J Nucl Med 1996;37:2002–2006PubMedGoogle Scholar
  71. 71.
    Ginj M, Hinni K, Tschumi S, Schulz S, Maecke HR. Trifunctional somatostatin-based derivatives designed for targeted radiotherapy using Auger electron emitters. J Nucl Med 2005;46:2097–2103PubMedGoogle Scholar
  72. 72.
    Capello A, Krenning E, Bernard B, Reubi JC, Breeman W, de Jong M. 111In-labelled somatostatin analogues in a rat tumour model: somatostatin receptor status and effects of peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2005;32:1288–1295PubMedGoogle Scholar
  73. 73.
    Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med 2005;46 Suppl 1:62S–66SPubMedGoogle Scholar
  74. 74.
    De Jong M, Valkema R, Jamar F, Kvols LK, Kwekkeboom DJ, Breeman WA, et al. Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. Semin Nucl Med 2002;32:133–140PubMedGoogle Scholar
  75. 75.
    Krenning EP, Kwekkeboom DJ, Valkema R, Pauwels S, Kvols LK, De Jong M. Peptide receptor radionuclide therapy. Ann N Y Acad Sci 2004;1014:234–245PubMedGoogle Scholar
  76. 76.
    Mester J, DeGoeij K, Sluyser M. Modulation of [5-125I]iododeoxyuridine incorporation into tumour and normal tissue DNA by methotrexate and thymidylate synthase inhibitors. Eur J Cancer 1996;32A:1603–1608PubMedGoogle Scholar
  77. 77.
    Kassis AI, Guptill WE, Taube RA, Adelstein SJ. Radiotoxicity of 5-[125I]iodo-2′-deoxyuridine in mammalian cells following treatment with 5-fluoro-2′-deoxyuridine. J Nucl Biol Med 1991;35:167–173PubMedGoogle Scholar
  78. 78.
    Lawrence TS, Davis MA, McKeever PE, Maybaum J, Stetson PL, Normolle DP, et al. Fluorodeoxyuridine-mediated modulation of iododeoxyuridine incorporation and radiosensitization in human colon cancer cells in vitro and in vivo. Cancer Res 1991;51:3900–3905PubMedGoogle Scholar
  79. 79.
    Dupertuis YM, Vazquez M, Mach JP, de Tribolet N, Pichard C, Slosman DO, et al. Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine. Cancer Res 2001;61:7971–7977PubMedGoogle Scholar
  80. 80.
    Buchegger F, Adamer F, Schaffland AO, Kosinski M, Grannavel C, Dupertuis YM, et al. Highly efficient DNA incorporation of intratumourally injected [125I]iododeoxyuridine under thymidine synthesis blocking in human glioblastoma xenografts. Int J Cancer 2004;110:145–149PubMedGoogle Scholar
  81. 81.
    Perillo-Adamer F, Bischof Delaloye A, Genton C, Schaffland AO, Dupertuis YM, Buchegger F. Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine. Eur J Nucl Med Mol Imaging 2006;33:613–620PubMedGoogle Scholar
  82. 82.
    Spears CP, Shahinian AH, Moran RG, Heidelberger C, Corbett TH. In vivo kinetics of thymidylate synthetase inhibition of 5-fluorouracil-sensitive and -resistant murine colon adenocarcinomas. Cancer Res 1982;42:450–456PubMedGoogle Scholar
  83. 83.
    Wilson WL, Bisel HF, Krementz ET, Lien RC, Prohaska JV. Further clinical evaluation of 2′-deoxy-5-fluorouridine (NSC-27640). Cancer Chemother Rep 1967;51:85–90PubMedGoogle Scholar
  84. 84.
    Serlin O, Wolkoff JS, Amadeo JM, Keehn RJ. Use of 5-fluorodeoxyuridine (FUDR) as an adjuvant to the surgical management of carcinoma of the stomach. Cancer 1969;24:223–228PubMedGoogle Scholar
  85. 85.
    Pressacco J, Mitrovski B, Erlichman C, Hedley DW. Effects of thymidylate synthase inhibition on thymidine kinase activity and nucleoside transporter expression. Cancer Res 1995;55:1505–1508PubMedGoogle Scholar
  86. 86.
    Valdes R, Casado FJ, Pastor-Anglada M. Cell-cycle-dependent regulation of CNT1, a concentrative nucleoside transporter involved in the uptake of cell-cycle-dependent nucleoside-derived anticancer drugs. Biochem Biophys Res Commun 2002;296:575–579PubMedGoogle Scholar
  87. 87.
    Sedelnikova OA, Panyutin IV, Neumann RD, Bonner WM, Panyutin IG. Assessment of DNA damage produced by 125I-triplex-forming oligonucleotides in cells. Int J Radiat Biol 2004;80:927–931PubMedGoogle Scholar
  88. 88.
    Panyutin IG, Winters TA, Feinendegen LE, Neumann RD. Development of DNA-based radiopharmaceuticals carrying Auger-electron emitters for anti-gene radiotherapy. Q J Nucl Med 2000;44:256–267PubMedGoogle Scholar
  89. 89.
    Cammilleri S, Sangrajrang S, Perdereau B, Brixy F, Calvo F, Bazin H. Biodistribution of iodine-125 tyramine transforming growth factor alpha antisense oligonucleotide in athymic mice with a human mammary tumour xenograft following intratumoral injection. Eur J Nucl Med 1996;23:448–452PubMedGoogle Scholar
  90. 90.
    He Y, Panyutin IG, Karavanov A, Demidov VV, Neumann RD. Sequence-specific DNA strand cleavage by 111In-labeled peptide nucleic acids. Eur J Nucl Med Mol Imaging 2004;31:837–845PubMedGoogle Scholar
  91. 91.
    Lee JF, Stovall GM, Ellington AD. Aptamer therapeutics advance. Curr Opin Chem Biol 2006;10:282–289PubMedGoogle Scholar
  92. 92.
    Lee JH, Canny MD, De EA, Krilleke D, Ng YS, Shima DT, et al. A therapeutic aptamer inhibits angiogenesis by specifically targeting the heparin binding domain of VEGF165. Proc Natl Acad Sci USA 2005;102:18902–18907PubMedGoogle Scholar
  93. 93.
    Farokhzad OC, Cheng J, Teply BA, Sherifi I, Jon S, Kantoff PW, et al. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci USA 2006;103:6315–6320PubMedGoogle Scholar
  94. 94.
    Hicke BJ, Stephens AW, Gould T, Chang YF, Lynott CK, Heil J, et al. Tumor targeting by an aptamer. J Nucl Med 2006;47:668–678PubMedGoogle Scholar
  95. 95.
    Pieken WA, Olsen DB, Benseler F, Aurup H, Eckstein F. Kinetic characterization of ribonuclease-resistant 2′-modified hammerhead ribozymes. Science 1991;253:314–317PubMedGoogle Scholar
  96. 96.
    Klussmann S, Nolte A, Bald R, Erdmann VA, Furste JP. Mirror-image RNA that binds D-adenosine. Nat Biotechnol 1996;14:1112–1115PubMedGoogle Scholar
  97. 97.
    Kim SJ, Kim MY, Lee JH, You JC, Jeong S. Selection and stabilization of the RNA aptamers against the human immunodeficiency virus type-1 nucleocapsid protein. Biochem Biophys Res Commun 2002;291:925–931PubMedGoogle Scholar
  98. 98.
    Welt S, Scott AM, Divgi CR, Kemeny NE, Finn RD, Daghighian F, et al. Phase I/II study of iodine 125-labeled monoclonal antibody A33 in patients with advanced colon cancer. J Clin Oncol 1996;14:1787–1797PubMedGoogle Scholar
  99. 99.
    Govindan SV, Goldenberg DM, Elsamra SE, Griffiths GL, Ong GL, Brechbiel MW, et al. Radionuclides linked to a CD74 antibody as therapeutic agents for B-cell lymphoma: comparison of Auger electron emitters with beta-particle emitters. J Nucl Med 2000;41:2089–2097PubMedGoogle Scholar
  100. 100.
    Michel RB, Rosario AV, Andrews PM, Goldenberg DM, Mattes MJ. Therapy of small subcutaneous B-lymphoma xenografts with antibodies conjugated to radionuclides emitting low-energy electrons. Clin Cancer Res 2005;11:777–786PubMedGoogle Scholar
  101. 101.
    Michel RB, Andrews PM, Castillo ME, Mattes MJ. In vitro cytotoxicity of carcinoma cells with 111In-labeled antibodies to HER-2. Mol Cancer Ther 2005;4:927–937PubMedGoogle Scholar
  102. 102.
    Michel RB, Brechbiel MW, Mattes MJ. A comparison of 4 radionuclides conjugated to antibodies for single-cell kill. J Nucl Med 2003;44:632–640PubMedGoogle Scholar
  103. 103.
    Hosono M, Hosono MN, Kraeber-Bodere F, Devys A, Thedrez P, Fiche M, et al. Biodistribution and dosimetric study in medullary thyroid cancer xenograft using bispecific antibody and iodine-125-labeled bivalent hapten. J Nucl Med 1998;39:1608–1613PubMedGoogle Scholar
  104. 104.
    Sisson JC. Radiopharmaceuticals for nuclear endocrinology at the University of Michigan. Cancer Biother Radiopharm 2000;15:305–318PubMedCrossRefGoogle Scholar
  105. 105.
    Sisson JC, Shapiro B, Hutchinson RJ, Shulkin BL, Zempel S. Survival of patients with neuroblastoma treated with 125-I MIBG. Am J Clin Oncol 1996;19:144–148Google Scholar
  106. 106.
    Bernhardt P, Forssell-Aronsson E, Jacobsson L, Skarnemark G. Low-energy electron emitters for targeted radiotherapy of small tumours. Acta Oncol 2001;40:602–608PubMedGoogle Scholar
  107. 107.
    Abdel-Nabi H, Ortman JA. Radiobiological effects of 131I and 125I on the DNA of the rat thyroid. I. Comparative study with emphasis on the postradiation hypothyroidism occurrence. Radiat Res 1983;93:525–533PubMedGoogle Scholar
  108. 108.
    Dradi C, Riceputi G, Biagioli R, Riva P. Radiotherapy with 131J and 125J of Basedow’s disease. Indications and results relative to the incidence of post-actinic hypothyroidism [in Italian]. Minerva Med 1979;70:135–141PubMedGoogle Scholar
  109. 109.
    McDougall IR, Greig WR, Gillespie FC. Iodine-125 therapy for thyrotoxicosis: background and evaluation in 148 patients. Strahlentherapie [Sonderb ] 1972;72:243–252Google Scholar
  110. 110.
    McDougall IR, Greig WR, Gray HW, Gillespie FC. Iodine-125 treatment for thyrotoxicosis. Lancet 1970;2:840–842PubMedGoogle Scholar
  111. 111.
    Gillespie FC, Orr JS, Greig WR. Microscopic dose distribution from 125-I in the toxic thyroid gland and its relation to therapy. Br J Radiol 1970;43:40–47PubMedCrossRefGoogle Scholar
  112. 112.
    Dwyer RM, Bergert ER, O’Connor MK, Gendler SJ, Morris JC. In vivo radioiodide imaging and treatment of breast cancer xenografts after MUC1-driven expression of the sodium iodide symporter. Clin Cancer Res 2005;11:1483–1489PubMedGoogle Scholar
  113. 113.
    Buchsbaum DJ, Chaudhuri TR, Zinn KR. Radiotargeted gene therapy. J Nucl Med 2005;46 Suppl 1:179S–186SPubMedGoogle Scholar
  114. 114.
    De Jong M, Valkema R, Van GA, Van BH, Bex A, Van De Weyer EP, et al. Inhomogeneous localization of radioactivity in the human kidney after injection of [111In-DTPA]octreotide. J Nucl Med 2004;45:1168–1171PubMedGoogle Scholar
  115. 115.
    Kassis AI, Tumeh SS, Wen PY, Baranowska-Kortylewicz J, Van den Abbeele AD, Zimmerman RE, et al. Intratumoral administration of 5-[123I]iodo-2’-deoxyuridine in a patient with a brain tumor. J Nucl Med 1996;37:19S–22SPubMedGoogle Scholar
  116. 116.
    Mariani G, Di Sacco S, Volterrani D, Di Luca L, Buralli S, Di Stefano R, et al. Tumor targeting by intra-arterial infusion of 5-[123I]iodo-2′- deoxyuridine in patients with liver metastases from colorectal cancer. J Nucl Med 1996;37:22S–25SPubMedGoogle Scholar
  117. 117.
    Mariani G, Di Sacco S, Bonini R, Di Luca L, Buralli S, Bonora D, et al. Biochemical modulation by 5-fluorouracil and 1-folinic acid of tumor uptake of intra-arterial 5-[123I]iodo-2′deoxyuridine in patients with liver metastases from colorectal cancer. Acta Oncol 1996;35:941–945PubMedGoogle Scholar
  118. 118.
    Bodei L, Kassis AI, Adelstein SJ, Mariani G. Radionuclide therapy with iodine-125 and other Auger-electron-emitting radionuclides: experimental models and clinical applications. Cancer Biother Radiopharm 2003;18:861–877PubMedGoogle Scholar
  119. 119.
    Xiao J, Horst S, Hinkle G, Cao X, Kocak E, Fang J, et al. Pharmacokinetics and clinical evaluation of 125I-radiolabeled humanized CC49 monoclonal antibody (HuCC49deltaC(H)2) in recurrent and metastatic colorectal cancer patients. Cancer Biother Radiopharm 2005;20:16–26PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Franz Buchegger
    • 1
    • 2
  • Florence Perillo-Adamer
    • 1
  • Yves M. Dupertuis
    • 3
  • Angelika Bischof Delaloye
    • 1
  1. 1.Service of Nuclear MedicineUniversity Hospital of Lausanne CHUVLausanneSwitzerland
  2. 2.Service of Nuclear MedicineUniversity Hospital of LausanneLausanneSwitzerland
  3. 3.Service of NutritionUniversity Hospital of GenevaGenevaSwitzerland

Personalised recommendations