Nuclear Medicine and Biology
Volume 34, Issue 8 , Pages 887-896 , November 2007

Effect of the EGFR density of breast cancer cells on nuclear importation, in vitro cytotoxicity, and tumor and normal-tissue uptake of [111In]DTPA-hEGF

Part of this work was presented at the Canadian Breast Cancer Research Alliance Reasons for Hope Conference, Montreal, Quebec, May 6–8, 2006.

  • Meiduo Hu

      Affiliations

    • Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada M5S 3M2
  • ,
  • Deborah Scollard

      Affiliations

    • Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada M5S 3M2
  • ,
  • Conrad Chan

      Affiliations

    • Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada M5S 3M2
  • ,
  • Paul Chen

      Affiliations

    • Neopharm, Inc., Waukegan, MI 60085-8328, USA
  • ,
  • Katherine Vallis

      Affiliations

    • Radiobiology Research Institute, University of Oxford, Oxford OX3 7LJ, UK
  • ,
  • Raymond M. Reilly

      Affiliations

    • Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada M5S 3M2
    • Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada M5G 1X5
    • Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada M5G 2C4
    • Corresponding Author InformationCorresponding author. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2. Tel.: +1 416 946 5522; fax: +1 416 978 8511.

Received 27 April 2007 ,Revised 15 June 2007 ,Accepted 25 June 2007.

References 

  1. Ro J, North SM, Gallick GE, et al. Amplified and overexpressed epidermal growth factor receptor gene in uncultured primary human breast carcinoma. Cancer Res. 1988;48:161–164
  2. Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12:5268–5272
  3. Sporn MB, Todaro GJ. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980;303:878–880
  4. Lo HW, Hsu SC, Hung MC. EGFR signaling pathways in breast cancers: from traditional signal transduction to direct nuclear translocalization. Breast Cancer Res Treat. 2005;95:211–218
  5. Lo HW, Hung MC. Nuclear EGFR signaling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. Br J Cancer. 2006;94:184–188
  6. Lo HW, Xia W, Wei Y, et al. Novel prognostic value of nuclear EGF receptor in breast cancer. Cancer Res. 2005;65:338–348
  7. Lo HW, Hsu SC, Ali-Seyed M, et al. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell. 2005;7:575–589
  8. Hanada N, Lo HW, Day CP, et al. Co-regulation of B-Myb expression by E2F1 and EGF receptor. Mol Carcinog. 2006;45:10–17
  9. Xu W, Liu LZ, Loizidou M, et al. The role of nitric oxide in cancer. Cell Res. 2002;12:311–320
  10. Lin SY, Makino K, Xia W, et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol. 2001;3:802–808
  11. Joaquin M, Watson RJ. Cell cycle regulation by the B-Myb transcription factor. Cell Mol Life Sci. 2003;60:2389–2401
  12. Lo HW, Ali-Seyed M, Wu Y, et al. Nuclear–cytoplasmic transport of EGFR involves receptor endocytosis, importin β1 and CRM1. J Cell Biochem. 2006;98:1570–1583
  13. Kassis AI. Cancer therapy with Auger electrons: are we almost there?. J Nucl Med. 2003;44:1479–1481
  14. Reilly RM, Scollard DA, Wang J, et al. A kit formulated under good manufacturing practices for labeling human epidermal growth factor with 111In for radiotherapeutic applications. J Nucl Med. 2004;45:701–708
  15. Reilly R, Kiarash R, Cameron R, et al. 111In-labeled EGF is selectively radiotoxic to human breast cancer cells overexpressing EGFR. J Nucl Med. 2000;41:429–438
  16. Chen P, Cameron R, Wang J, et al. Antitumour 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;44:1469–1478
  17. Dunn WA, Hubbard AL. Receptor-mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver: ligand and receptor dynamics. J Cell Biol. 1984;98:2148–2159
  18. Reilly R, Chen P, Wang J, et al. Preclinical pharmacokinetic, biodistribution, toxicology, and dosimetry studies of 111In-DTPA-human epidermal growth factor: an Auger electron-emitting radiotherapeutic agent for epidermal growth factor receptor-positive breast cancer. J Nucl Med. 2006;47:1023–1031
  19. Reilly RM, Kiarash R, Sandhu J, et al. A comparison of EGF and mAb 528 labeled with 111In for imaging human breast cancer. J Nucl Med. 2000;41:903–911
  20. Hu M, Chen P, Wang J, et al. Site-specific conjugation of HIV-1 tat peptides to IgG: a potential route to construct radioimmunoconjugates for targeting intracellular and nuclear epitopes in cancer. Eur J Nucl Med Mol Imaging. 2006;33:301–310
  21. Reilly R. Biomolecules as targeting vehicles for in situ radiotherapy of malignancies. In:  Knaeblein J editors. Modern biopharmaceuticals: design, development and optimization. Vol. 2:Weinheim, Germany: Wiley-VCH; 2005;p. 497–526
  22. Tolmachev V, Orlova A, Wei Q, et al. Comparative biodistribution of potential anti-glioblastoma conjugates [111In]DTPA-hEGF and [111In]BZ-DTPA-hEGF in normal mice. Cancer Biother Radiopharm. 2004;19:491–501

PII: S0969-8051(07)00175-8

doi: 10.1016/j.nucmedbio.2007.06.010

Nuclear Medicine and Biology
Volume 34, Issue 8 , Pages 887-896 , November 2007