Journal of Neuro-Oncology

, Volume 77, Issue 1, pp 33–45 | Cite as

Planning for Intracavitary Anti-EGFR Radionuclide Therapy of Gliomas. Literature Review and Data on EGFR Expression

  • Carlsson J
  • Ren Z.P
  • Wester K
  • Sundberg Å.L
  • Heldin N.E
  • Hesselager G
  • Persson M
  • Gedda L
  • Tolmachev V
  • Lundqvist H
  • Blomquist E
  • Nistér M
Clinical Study


Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.


EGFR glioma intracavitary locoregional radionuclide therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    ME Berens and A Giese, “…those left behind.” Biology and oncology of invasive glioma cells. Neoplasia 1 (1999) 208-219CrossRefPubMedGoogle Scholar
  2. 2.
    AJ Bolteus, ME Berens and GJ Pilkington, Migration and invasion in brain neoplasms. Curr Neurol Neurosci Rep 1 (2001) 225-232PubMedCrossRefGoogle Scholar
  3. 3.
    A Giese, R Bjerkvig, ME Berens and M Westphal, Cost of migration: invasion of malignant gliomas, implications for treatment. J Clin Oncol. 21 (2003) 1624-1636CrossRefPubMedGoogle Scholar
  4. 4.
    JN Rich and DD Bigner, Development of novel targeted therapies in the treatment of malignant glioma. Nat Rev Drug Discov 3 (2004) 430-446CrossRefPubMedGoogle Scholar
  5. 5.
    R Benjamin, J Capparella and A Brown, Classification of glioblastoma multiforme in adults by molecular genetics. Cancer J 9 (2003) 82-90PubMedCrossRefGoogle Scholar
  6. 6.
    TA Libermann, HR Nusbaum, N Razon, R Kris, I Lax, H Soreq, N Whittle, MD Waterfield, A Ullrich and J Schlessinger, Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313 (1985) 144-147CrossRefPubMedADSGoogle Scholar
  7. 7.
    P Kleihues and H Ohgaki, Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncol 1 (1999) 44-51CrossRefPubMedGoogle Scholar
  8. 8.
    P Kleihues and H Ohgaki, Phenotype vs genotype in the evolution of astrocytic brain tumors. Toxicol Pathol 28 (2000) 164-170PubMedGoogle Scholar
  9. 9.
    A Boskovitz, CJ Wikstrand, CT Kuan, MR Zalutsky, DA Reardon and DD Bigner, Monoclonal antibodies for brain tumour treatment. Expert Opin Biol Ther 4 (2004) 1453-1471CrossRefPubMedGoogle Scholar
  10. 10.
    J Schlegel, A Merdes, G Stumm, FK Albert, M Forsting, N Hynes and M Kiessling, Amplification of the epidermal-growth-factor-receptor gene correlates with different growth behaviour in human glioblastoma. Int J Cancer 56 (1994) 72-77PubMedCrossRefGoogle Scholar
  11. 11.
    CJ Wikstrand and DD Bigner, Prognostic applications of the epidermal growth factor receptor and its ligand, transforming growth factor-alpha. J Natl Cancer Inst 90 (1998) 799-801CrossRefPubMedGoogle Scholar
  12. 12.
    N Shinojima, K Tada, S Shiraishi, T Kamiryo, M Kochi, H Nakamura, K Makino, H Saya, H Hirano, J Kuratsu, K Oka, Y Ishimaru and Y Ushio, Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res 63 (2003) 6962-6970PubMedGoogle Scholar
  13. 13.
    Y Okada, EE Hurwitz, JM Esposito, MA Brower, CL Nutt and DN Louis, Selection pressures of TP53 mutation and microenvironmental location influence epidermal growth factor receptor gene amplification in human glioblastomas. Cancer Res 63 (2003) 413-416PubMedGoogle Scholar
  14. 14.
    AJ Ekstrand, CD James, WK Cavenee, B Seliger, RF Pettersson and VP Collins, Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 51 (1991) 2164-2172PubMedGoogle Scholar
  15. 15.
    O Lang, E Liebermeister, J Liesegang and ML Sautter-Bihl, Radiotherapy of glioblastoma multiforme: feasibility of increased fraction size and shortened overall treatment. Strahlenther? Onkol 174 (1998) 629-632PubMedCrossRefGoogle Scholar
  16. 16.
    FG Barker 2nd, SM Chang, PH Gutin, MK Malec, MW McDermott, MD Prados and CB Wilson, Survival, functional status after resection of recurrent glioblastoma multiforme. Neurosurgery 42 (1998) 709-720CrossRefPubMedGoogle Scholar
  17. 17.
    ML Simmons, KR Lamborn, M Takahashi, P Chen, MA Israel, MS Berger, T Godfrey, J Nigro, M Prados, S Chang, FG Barker 2nd and K Aldape, Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients. Cancer Res 61 (2001) 1122-1128PubMedGoogle Scholar
  18. 18.
    R Stupp, WP Mason, MJ van den Bent, M Weller, B Fisher, MJ Taphoorn, K Belanger, AA Brandes, C Marosi and U Bogdahn, Radiotheraphy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (2005) 987-996CrossRefPubMedGoogle Scholar
  19. 19.
    K Kiya, T Uozumi, H Ogasawara, K Sugiyama, T Hotta, T Mikami and K Kurisu, Penetration of etoposide into human malignant brain tumors after intravenous and oral administration. Cancer Chemother Pharmacol 29 (1992) 339-342CrossRefPubMedGoogle Scholar
  20. 20.
    A Boiardi, A Silvani, A Pozzi, L Fariselli, G Broggi and A Salmaggi, Interstitial chemotherapy plus systemic chemotherapy for glioblastoma patients: improved survival in sequential studies. J Neurooncol 41 (1999) 151-157CrossRefPubMedGoogle Scholar
  21. 21.
    E Blomquist and J Carlsson, Strategy for planned radiotherapy of malignant gliomas. Postoperative treatments with high dose proton irradiation and tumor seeking radionuclides. Int J Radiat Oncol Biol Phys 22 (1991) 259-263Google Scholar
  22. 22.
    MR Zalutsky, Targeted radiotherapy of brain tumours. Br J Cancer 90 (2004) 1469-1473CrossRefPubMedGoogle Scholar
  23. 23.
    AA Epenetos, N Courtenay-Luck, D Pickering, G Hooker, H Durbin, JP Lavender and CG McKenzie, Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen. Br Med J (Clin Res Ed) 290 (1985) 1463-1466CrossRefGoogle Scholar
  24. 24.
    HP Kalofonos, TR Pawlikowska, A Hemingway, N Courtenay-Luck, B Dhokia, D Snook, GB Sivolapenko, GR Hooker, CG McKenzie and PJ Lavender, Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase. J Nucl Med 30 (1989) 1636-1645PubMedGoogle Scholar
  25. 25.
    LW Brady, C Miyamoto, DV Woo, M Rackover, J Emrich, H Bender, S Dadparvar, Z Steplewski, H Koprowski and P Black, Malignant astrocytomas treated with iodine−125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial. Int J Radiat Oncol Biol Phys 22 (1992) 225-230PubMedGoogle Scholar
  26. 26.
    JG Emrich, LW Brady, TS Quang, R Class, C Miyamoto, P Black and U Rodeck, Radioiodinated (I−125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment. Am J Clin Oncol 25 (2002) 541-546CrossRefPubMedGoogle Scholar
  27. 27.
    J Schlessinger, Cell signaling by receptor tyrosine kinases. Cell 103 (2000) 211-25CrossRefPubMedGoogle Scholar
  28. 28.
    MA Olayioye, RM Neve, HA Lane and NE Hynes, The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19 (2000) 3159-3167CrossRefPubMedGoogle Scholar
  29. 29.
    Y Yarden and MX Sliwkowski, Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2 (2001) 127-137CrossRefPubMedGoogle Scholar
  30. 30.
    ZR Shi, SH Itzkowitz and YS Kim, A comparison of three immunoperoxidase techniques for antigen detection in colorectal carcinoma tissues. J Histochem Cytochem 36 (1988) 317-322PubMedGoogle Scholar
  31. 31.
    AJ Norton, S Jordan and P Yeomans, Brief, high-temperature heat denaturation (pressure cooking): a simple and effective method of antigen retrieval for routinely processed tissues. J Pathol 173 (1994) 371-379CrossRefPubMedGoogle Scholar
  32. 32.
    L Ohman, L Gedda, G Hesselager, R Larsson, M Nister, T Stigbrand, K Wester and J Carlsson, A new antibody recognizing the vIII mutation of human epidermal growth factor receptor. Tumour Biol. 23 (2002) 61-69CrossRefPubMedGoogle Scholar
  33. 33.
    A Waha, B Rollbrocker, OD Wiestler and A Deimling von, A polymerase chain reaction-based assay for the rapid detection of gene amplification in human tumors. Diagn Moll Pathol 5 (1996) 147-150CrossRefGoogle Scholar
  34. 34.
    JD Bergstrom, A Hermansson, T Diaz Ståhl de and N-E Heldin, Non-autocrine, constitutive activation of Met in human anaplastic thyroid carcinoma cells in culture. Br J Cancer 80 (1999) 650-656CrossRefPubMedGoogle Scholar
  35. 35.
    M Hermansson, M Nister, C Betsholtz, CH Heldin, B Westermark and K Funa, Endothelial cell hyperplasia in human glioblastoma: coexpression of mRNA for platelet-derived growth factor (PDGF) B chain and PDGF receptor suggests autocrine growth stimulation. Proc Natl Acad Sci USA 85 (1988) 7748-7752PubMedADSCrossRefGoogle Scholar
  36. 36.
    L Uhrbom, G Hesselager, M Nister and B Westermark, Induction of brain tumors in mice using a recombinant platelet-derived growth factor 13−chain retrovirus. Cancer Res 58 (1998) 5275-5279PubMedGoogle Scholar
  37. 37.
    K Khazaie, V Schirrmacher and RB Lichtner, EGF receptor in neoplasia and metastasis. Cancer Metastasis Rev 12 (1993) 255-274CrossRefPubMedGoogle Scholar
  38. 38.
    DA Reardon, G Akabani, RE Coleman, AH Friedman, HS Friedman, JE Herndon 2nd, I Cokgor, RE McLendon, CN Pegram, JM Provenzale, JA Quinn, JN Rich, LV Regalado, JH Sampson, TD Shabnan, CJ Wikstrand, TZ Wong, XG Zhao, MR Zalutsky and DD Bigner, Phase II trial of murine (131)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant glomas. J Clin Oncol 20 (2002) 1389-1397CrossRefPubMedGoogle Scholar
  39. 39.
    P Riva, G Franceschi, N Riva, M Casi, M Santimaria and M Adamo, Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach. Eur J Nucl Med 27 (2000) 601-609CrossRefPubMedGoogle Scholar
  40. 40.
    C Goetz, P Riva, G Poepperl, FJ Gildehaus, A Hischa, K Tatsch and HJ Reulen, Locoregional radioimmunotherapy in selected patients with maligant gliomas: experiences, side effects, survival times. J Neurooncol 62 (2003) 321-0328CrossRefPubMedGoogle Scholar
  41. 41.
    G Paganelli, M Bartolomei, M Ferrari, M Cremonesi, G Broggi, G Maira, C Sturiale, C Gana, G Prisco, M Gatti, P Caliceti and M Chinol, Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients: phase I study and preliminary therapeutic results. Cancer Biother Radiopharm 16 (2001) 227-235CrossRefPubMedGoogle Scholar
  42. 42.
    M Bartolomei, C Mazzetta, D Handkiewicz-Junak, L Bodei, P Rocca, C Grana, G Maira, C Sturiale, G Villa and G Paganelli, Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and temozolomide. Q J Nucl Med Mol Imaging 48 (2004) 220-228PubMedGoogle Scholar
  43. 43.
    A Merlo, O Hausmann, M Wasner, P Steiner, A Otte, E Jerrnann, P Freitag, JC Reubi, J Muller-Brand, O Gratzl and HR Macke, Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phel-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas. Clin Cancer Res 5 (1999) 1025-1033PubMedGoogle Scholar
  44. 44.
    T Schumacher, S Hofer, K Eichhorn, M Wasner, S Zimmerer, P Freitag, A Probst, O Gratzl, JC Reubi, R Maecke, J Mueller-Brand and A Merlo, Local injection of the 90Y-labelled peptidic vector DOTATOC to control gliomas of WHO grades II and III: an extended pilot study. Eur J Nucl Med Mol Imaging 29 (2002) 486-493CrossRefPubMedGoogle Scholar
  45. 45.
    A Merlo, J Mueller-Brand and HR Maecke, Comparing monoclonal antibodies and small peptidic hormones for local targeting of malignant gliomas. Acta Neurochir Suppl 88 (2003) 83-91PubMedGoogle Scholar
  46. 46.
    K Fujimori, DG Covell, JE Fletcher and JN Weinstein, A modeling analysis of monoclonal antibody percolation through tumors: a binding-site barrier. J Nucl Med 31 (1990) 1191-1198PubMedGoogle Scholar
  47. 47.
    M Juweid, R Neumann, C Paik, MJ Perez-Bacete, J Sato, W Osdol van and JN Weinstein, Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier. Cancer Res 52 (1992) 5144-5153PubMedGoogle Scholar
  48. 48.
    A Lindstrom and J Carlsson, Penetration and binding of epidermal growth factor-dextran conjugates in spheroids of human glioma origin. Cancer Biotherapy 8 (1993) 145-158PubMedGoogle Scholar
  49. 49.
    GP Adams, R Schier, AM McCall, HH Simmons, EM Horak, RK Alpaugh, JD Marks and LM Weiner, High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules. Cancer Res 61 (2001) 4750-4755PubMedGoogle Scholar
  50. 50.
    W Yang, RF Barth, DM Adams and AH Soloway, Intratumoral delivery of boronated epidermal growth factor for neutron capture therapy of brain tumors. Cancer Res 57 (1997) 4333-4339PubMedGoogle Scholar
  51. 51.
    P Olsson, L Gedda, H Goike, L Liu, VP Collins, J Pontén and J Carlsson, Uptake of a boronated epidermal growth factor-dextran conjugate in CHO xenografts with and without human EGF-receptor expression. Anti-Cancer Drug Design 13 (1998) 279-289PubMedGoogle Scholar
  52. 52.
    G Wu, RF Barth, W Yang, M Chatterjee, W Tjarks, MJ Ciesielski and RA Fenstermaker, Sitespecific conjugation of boron-containing dendrimers to anti-EGF receptor monoclonal antibody cetuximab (IMC-C225) and its evaluation as a potential delivery agent for neutron capture therapy. Bioconjug Chem 15 (2004) 185-194CrossRefPubMedGoogle Scholar
  53. 53.
    CJ Wikstrand, LP Hale, SK Batra, ML Hill, PA Humphrey, SN Kurpad, RE McLendon, D Moscatello, CN Pegram and CJ Reist, Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res 55 (1995) 3140-3148PubMedGoogle Scholar
  54. 54.
    HS Huang, M Nagane, CK Kingbeil, H Lin, R Nishikawa, XD Ji, CM Huang, GN Gill, HS Wiley and WK Cavenee, The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J Biol Chem 272 (1997) 2927-2935CrossRefPubMedGoogle Scholar
  55. 55.
    CT Kuan, CJ Wikstrand and DD Bigner, EGF mutant receptor vIII as a molecular target in cancer therapy. Endocr Relat Cancer 8 (2001) 83-96CrossRefPubMedGoogle Scholar
  56. 56.
    CJ Wikstrand, RE McLendon, AH Friedman and DD Bigner, Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor. EGFRvIII Cancer Res 57 (1997) 4130-4140Google Scholar
  57. 57.
    AJ Ekstrand, L Liu, J He, ML Harnid, N Longo, VP Collins and CD James, Altered subcellular location of an activated and tumour-associated epidermal growth factor receptor. Oncogene 10 (1995) 1455-60PubMedGoogle Scholar
  58. 58.
    RL Gutman, G Peacock and DR Lu, Targeted drug delivery for brain cancer treatment. J Control Release 65 (2000) 31-41CrossRefPubMedGoogle Scholar
  59. 59.
    M Westphal, K Lamszus and D Hilt, Intracavitary chemotherapy for glioblastoma: present status and future directions. Acta Neurochir Suppl 88 (2003) 61-67PubMedGoogle Scholar
  60. 60.
    M Westphal, DC Hilt, E Bortey, P Delavault, R Olivares, PC Warlike, IR Whittle, J Jaaskelainen and Z Ram, A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neurooncology 5 (2003) 79-88Google Scholar
  61. 61.
    A Giese, T Kucinski, U Knopp, R Goldbrunner, W Hamel, HM Mehdorn, JC Tonn, D Hilt and M Westphal, Pattern of recurrence following local chemotherapy with biodegradable carmustine (BCNU) implants in patients with glioblastoma. J Neurooncol 66 (2004) 351-360CrossRefPubMedGoogle Scholar
  62. 62.
    J Carlsson, E Forssell Aronsson, B Glilnelius and S Mattsson, Therapy with radiopharmaceuticals. Acta Oncol 41 (2002) 623-628CrossRefPubMedGoogle Scholar
  63. 63.
    J Carlsson, E Forssell Aronsson, SO Hietala, T Stigbrand and J Tennvall, Tumour therapy with radionuclides; assessment of progress and problems. Radiother Oncol 66 (2003) 107-117CrossRefPubMedGoogle Scholar
  64. 64.
    DM Goldenberg, Advancing role of radiolabeled antibodies in the therapy of cancer. Cancer Immunol lmmunother 52 (2003) 281-296Google Scholar
  65. 65.
    B Gusterson, G Cowley, JA Smith and B Ozanne, Cellular localisation of human epidermal growth factor receptor. Cell Biol lnt Rep 8 (1984) 649-658CrossRefGoogle Scholar
  66. 66.
    I Damjanov, B Mildner and BB Knowles, Immunohistochemical localization of the epidermal growth factor receptor in normal human tissues. Lab Invest 55 (1986) 588-592PubMedGoogle Scholar
  67. 67.
    Q Zhao, E Blomquist, H Bolander, L Gedda, P Hartvig, JC Jansson, H Lundqvist, H Mellstedt, S Nilsson, M Nistér, A Sundin, V Tohmachev, JE Westlin and J Carlsson, Conjugate chemistry, iodination and cellular binding of mEGF-dextran-tyrosine Preclinical tests in preparation for clinical trials. Int J Mol Med 1 (1998) 693-702PubMedGoogle Scholar
  68. 68.
    AL Sundberg, A Orlova, A Bruskin, L Gedda, J Carlsson and V Tohnachev, 111-In-Bz-DTPA-hEGF: preparation and in vitro characterisation of a potential anti-glioblastoma targeting peptide. Cancer Biother Radiopharm 18 (2003) 643-654CrossRefPubMedGoogle Scholar
  69. 69.
    AL Sundberg, L Gedda, A Orlova, A Bruskin, E Blomquist, J Carlsson and V Tolmachev, [177Lu] Bz-DTPA-EGF: preclinical characterization of a potential radionuclide targeting agent against glioma. Cancer Biother Radiopharm 19 (2004) 195-204CrossRefPubMedGoogle Scholar
  70. 70.
    S Scott-Robson, J Capala, J Carlsson, P Malmborg and H Lundqvist, Distribution and stability in the rat of a 76-Br1125-I labelled polypeptide, epidermal growth factor. Int J Appl Radiat Isotopes Nucl Med Biol 18 (1991) 241-246Google Scholar
  71. 71.
    A Lovqvist, A Lindstrom and J Carlsson, Binding, internalization and excretion of TGFalfadextran associated radioactivity in cultured human glioma cells. Cancer Biother 8 (1993) 345-356PubMedGoogle Scholar
  72. 72.
    J Capala, RF Barth, MQ Bailey, RA Fenstermaker, MJ Marek and BA Rhodes, Radiolabeling of epidermal growth factor with 99mTc and in vivo localization following intracerebral injection into normal and glioma-bearing rats. Bioconjug Chem 8 (1997) 289-295CrossRefPubMedGoogle Scholar
  73. 73.
    M Rusckowski, T Qu, F Chang and DJ Hnatowich, Technetium−99m labeled epidermal growth factor-tumor imaging in mice. J Pept Res 50 (1997) 393-401PubMedCrossRefGoogle Scholar
  74. 74.
    A Kurihara, Y Deguchi and WM Pardridge, Epidermal growth factor radiopharmaceuticals: 111In chelation, conjugation to a blood–brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors. Bioconjug Chem 1999 10 (1999) 502-511CrossRefGoogle Scholar
  75. 75.
    W Yang, RF Barth, R Leveille, DM Adams, M Ciesielski, RA Fenstermaker and J Capala, Evaluation of systemically administered radiolabeled epidermal growth factor as a brain tumor targeting agent. J Neurooncol 55 (2001) 19-28CrossRefPubMedGoogle Scholar
  76. 76.
    J Capala, M Pråhl, S Scott-Robson, J Pontén, B Westennark and J Carlsson, Effects of 131-I-EGF on cultured human glioma cells. J Neuro-Oncol 9 (1990) 201-210CrossRefGoogle Scholar
  77. 77.
    J Capala and J Carlsson, Influence of chloroquine and lidocaine on the therapeutical effects of 131-I-EGF.Studies on cultured glioma cells. Int J. Radiat Biol 60 (1991) 497-510PubMedCrossRefGoogle Scholar
  78. 78.
    A Andersson, J Capala and J Carlsson, Effects of EGF-dextran-tyrosine−131-I conjugates on the clonogenic survival of cultured glioma cells. J Neuro-Oncol 14 (1992) 213-223CrossRefGoogle Scholar
  79. 79.
    J Carlsson, E Blomquist, L Gedda, Å Liljegren, PU Malmström, A Sjöström, A Sundin, V Tolimachev, JE Westlin, Q Zhao and H Lundqvist, Conjugate chemistry and cellular processing of EGF-dextran. Acta Oncol 38 (1999) 313-321CrossRefPubMedGoogle Scholar
  80. 80.
    P Chen, M Mrkobrada, KA Vallis, R Cameron, J Sandhu, A Hendler and RM Reilly, Comparative antiproliferative effects of (111)ln-DTPA-IEGF, chemotherapeutic agents and gamma-radiation on EGFR-positive breast cancer cells. Nucl Med Biol 29 (2002) 693-699CrossRefPubMedGoogle Scholar
  81. 81.
    P Chen, R Cameron, J Wang, KA Vallis and RM Reilly, 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 44 (2003) 1469-1478PubMedGoogle Scholar
  82. 82.
    AL Sundberg, E Blomquist, J Carlsson, AC Steffen and L Gedda, Cellular retention of radioactivity and increased radiation dose. Model experiments with EGF-dextran. Mel Med Biol 30 (2003) 303-315Google Scholar
  83. 83.
    AL Sundberg, Y Almqvist, A Orlova, E Blomquist, HJ Jensen, L Gedda, V Tolmachev and J Carlsson, Combined effect of gefitinib (‘Iressa’, ZD1839) and targeted radiotherapy with 211At-EGF. Eur J Nucl Med Mol Imaging 30 (2003) 1348-1356CrossRefPubMedGoogle Scholar
  84. 84.
    V Tolmachev, A Orlova, Q Wei, A Bruskin, J Carlsson and L Gedda, Comparative biodistribution of potential anti-glioblastoma conjugates [(1 11)In]DTPA-hEGF and [(111)In]Bz-DTPA-hEGF in normal mice. Cancer Biother Radiopharm 19 (2004) 491-501PubMedGoogle Scholar
  85. 85.
    C Schatten, N Pateisky, N Vavra, P Ehrenbock, P Angelberger, G Sivolapenko and A Epenetos, Lymphoscintigraphy with 123I-labelled epidermal growth factor. Lancet 337 (1991) 395-396CrossRefPubMedGoogle Scholar
  86. 86.
    A Cuartero-Plaza, E Martinez-Miralles, R Rosell, C Vadell-Nadal, M Farre and FX Real, Radiolocalization of squamous lung carcinoma with 131I-labeled epidermal growth factor. Clin Cancer Res 2 (1996) 13-20PubMedGoogle Scholar
  87. 87.
    P Bue, AR Holmberg, M Marquez, JE Westlin, S Nilsson and PU Malmstrom, Intravesical administration of EGF-dextran conjugates in patients with superficial bladder cancer. Eur Urol 38 (2000) 584-589CrossRefPubMedGoogle Scholar
  88. 88.
    RM Reilly, DA Scollard, J Wang, H Mondal, P Chen, LA Henderson, BM Bowen and KA Vallis, A kit formulated under good manufacturing practices for labeling human epidermal growth factor with 111In for radiotherapeutic applications. J Nucl Med 45 (2004) 701-708PubMedGoogle Scholar
  89. 89.
    ID Campbell, RM Cooke, M Baron, TS Harvey and MJ Tappin, The solution structures of epidermal growth factor and transforming growth factor alpha. Prog Growth Factor Res 1 (1989) 13-22CrossRefPubMedGoogle Scholar
  90. 90.
    A Orlova, A Bruskin, A Sjostrom, H Lundqvist, L Gedda and V Tolmachev, Cellular processing of (125)I- and (111)In-labeled epidermal growth factor (EGF) bound to cultured A431 tumor cells. Nucl Med Biol 27 (2000) 827-835CrossRefPubMedGoogle Scholar
  91. 91.
    Q Zhao, V Tolmachev, J Carlsson, H Lundqvist, J Sundin, JC Janson and A Sundin, Effects of dextranation on the pharmacokinetics of short peptides A PET study on mEGF. Bioconjugate Chem 10 (1999) 938-946CrossRefGoogle Scholar
  92. 92.
    M Hagg, Å Liljegren, J Carlsson, L Rönnstrand and J Lennartsson, EGF and dextran-conjugated EGF induces differential phosphorylation of the EGF receptor. Int J Mol Med 10 (2002) 655-659PubMedGoogle Scholar
  93. 93.
    SK Imam, Advancements in cancer therapy with alpha-emitters: a review. Int J Radiat Oncol Biol Phys 51 (2001) 271-278CrossRefPubMedGoogle Scholar
  94. 94.
    MR Zalutsky and G Vaidyanathan, Astatine−211-labeled radiotherapeutics: an emerging approach to targeted alpha-particle radiotherapy. Curr Pharm Des 6 (2000) 1433-1455CrossRefPubMedGoogle Scholar
  95. 95.
    MR Zalutsky, Current status of therapy of solid tumors: brain tumor therapy. J Nucl Med 46 (2005) 151S-156SPubMedGoogle Scholar
  96. 96.
    JA O’Donoghue, M Bardies and TE Wheldon, Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med 3 (1995) 1902-1909Google Scholar
  97. 97.
    T Hartman, H Lundqvist, JE Westlin and J Carlsson, Radiation doses to the cell nucleus in single cells and cells in micrometastasis in radionuclide therapy with 131-I labelled ligands or antibodies. lnt J Radiat Biol Phys 46 (2000) 1025-1036CrossRefGoogle Scholar
  98. 98.
    MJ Mattes, Radionuclide-antibody conjugates for single-cell cytotoxicity. Cancer 94 (2002) 1215-1223CrossRefPubMedGoogle Scholar
  99. 99.
    R Stein, SV Govindan, S Chen, L Reed, H Richel, GL Griffiths, HJ Hansen and DM Goldenberg, Radioimmunotherapy of a human lung cancer xenograft with monoclonal antibody RS7: evaluation of (177)Lu and comparison of its efficacy with that of (90)Y and residualizing (131) I. J Nucl Med 42 (2001) 967-974PubMedGoogle Scholar
  100. 100.
    DJ Kwekkeboom, WH Bakker, PP Kooij, MW Konijnenberg, A Srinivasan, JL Erion, MA Schmidt, JL Bugaj, M de Jong and EP Krenning, [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. Eur J Nucl Med 28 (2001) 1319-1325CrossRefPubMedGoogle Scholar
  101. 101.
    JA O’Donoghue and TE Wheldon, Targeted radiotherapy using Auger electron emitters. Phys Med Biol 41 (1996) 1973-1992CrossRefPubMedGoogle Scholar
  102. 102.
    AI Kassis, Cancer therapy with Auger electrons: are we almost there?. J Nucl Med 44 (2003) 1479-1481PubMedGoogle Scholar
  103. 103.
    TM Behr, M Behe, M Lohr, G Sgouros, C Angerstein, E Wehrmann, K Nebendahl and W Becker, Therapeutic advantages of Auger electron- over beta-emitting radiometals or radioiodine when conjugated to internalizing antibodies. Eur J Nucl Med 27 (2000) 753-765CrossRefPubMedGoogle Scholar
  104. 104.
    RM Reilly, R Kiarash, RG Cameron, N Porlier, J Sandhu, RP Hill, K Vallis, A Hendler and J Gariepy, 111In-labeled EGF is selectively radiotoxic to human breast cancer cells overexpressing EGFR. J Nucl Med 41 (2000) 429-438PubMedGoogle Scholar
  105. 105.
    EP Krenning, DJ Kwekkeboom, R Valkema, S Pauwels, LK Kvols and M Jong De, Peptide receptor radionuclide therapy. Ann N Y Acad Sci 1014 (2004) 234-245CrossRefPubMedADSGoogle Scholar
  106. 106.
    JR Buscombe and K Pigott, New approaches in targeting intracerebral tumours with 90Y-labelled radiopeptides. Eur J Nucl Med Mol Imaging 29 (2002) 1697-1698CrossRefPubMedGoogle Scholar
  107. 107.
    DM Goldenberg, Targeted therapy of cancer with radiolabeled antibodies. J Nucl Med 43 (2002) 693-713PubMedGoogle Scholar
  108. 108.
    J Baselga, The EGFR as a target for anticancer therapy––focus on cetuximab. Eur J Cancer 37 (2001) S16-22CrossRefPubMedGoogle Scholar
  109. 109.
    M Ranson, Technology evaluation: ABX-EGF, Abgenix/Amgen. Curr Opin Mol Ther 5 (2003) 541-546PubMedGoogle Scholar
  110. 110.
    RS Herbst, M Fukuoka and J Baselga, Gefitinib––a novel .targeted approach to treating cancer. Nat Rev Cancer 4 (2004) 956-965CrossRefPubMedGoogle Scholar
  111. 111.
    P Krozely, Epidermal growth factor receptor tyrosine kinase inhibitors: evolving role in the treatment of solid tumors. Clin J Oncol Nurs 8 (2004) 163-168PubMedCrossRefGoogle Scholar
  112. 112.
    AJ Wong, SH Bigner, DD Bigner, KW Kinzler, SR Hamilton and B Vogelstein, Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci USA 84 (1987) 6899-6903PubMedADSCrossRefGoogle Scholar
  113. 113.
    A Merlo, E Jermann, O. R Hausmann Chiquet-Ehrismann, A Probst, H Landolt, HR Maecke, J Mueller-Brand and O Gratzl, Biodistribution of 111In-labelled SCN-bz-DTPA-BC−2 MAb following loco-regional injection into glioblastomas. Int J Cancer 71 (1997) 810-816CrossRefPubMedGoogle Scholar
  114. 114.
    C Walker, DG du Plessis, KA Joyce, Y Machell, J Thomson-Hehir, SA Al Haddad, JC Broome and PC Warnke, Phenotype versus genotype in gliomas displaying inter- or intratumoral histological heterogeneity. Clin Cancer Res 9 (2003) 4841-4851PubMedGoogle Scholar
  115. 115.
    JS Bertram, The molecular biology of cancer. Mol Aspects Med 21 (2000) 167-223CrossRefPubMedGoogle Scholar
  116. 116.
    P Bue, K Wester, A Sjostrom, A Holmberg, S Nilsson, J Carlsson, C Busch, JE Westlin and PU Malmstrom, Expression of epidermal growth factor receptor in urinary bladder cancer metastasis. Int J Cancer 76 (1998) 189-193CrossRefPubMedGoogle Scholar
  117. 117.
    K Wester, A Sjostrom, M la Torre de, J Carlsson and PU Malmstrom, HER−2––a possible target for therapy of metastatic urinary bladder carcinoma. Acta Oncol 41 (2002) 282-288CrossRefPubMedGoogle Scholar
  118. 118.
    J Carlsson, H Nordgren, J Sjostrom, K Wester, K Villman, NO Bengtsson, B Ostenstad, H Lundqvist and C Blomqvist, HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review. Br J Cancer 90 (2004) 2344-2348PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Carlsson J
    • 1
  • Ren Z.P
    • 2
  • Wester K
    • 1
  • Sundberg Å.L
    • 1
  • Heldin N.E
    • 2
  • Hesselager G
    • 3
  • Persson M
    • 1
  • Gedda L
    • 1
  • Tolmachev V
    • 1
  • Lundqvist H
    • 1
  • Blomquist E
    • 1
  • Nistér M
    • 2
    • 4
  1. 1.Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical ImmunologyRudbeck Laboratory, Uppsala UniversityUppsalaSweden
  2. 2.Unit of Molecular Pathology, Department of Genetics and PathologyRudbeck Laboratory, Uppsala UniversityUppsalaSweden
  3. 3.Unit of Neurosurgery, Department of NeuroscienceUppsala University HospitalUppsalaSweden
  4. 4.Department of Oncology PathologyCancer Centre Karolinska, Karolinska Institutet, Karolinska University Hospital - SolnaStockholmSweden

Personalised recommendations