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Immunoglobulins as Radiopharmaceutical Vectors

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Radiopharmaceutical Chemistry

Abstract

With the introduction of the magic bullet concept by Ehrlich and the subsequent development of hybridoma technology by Kohler and Milstein, the world of target-specific protein-based drugs was opened. Since then, numerous immunoglobulins and a few dozen radioimmunoconjugates have been approved by the US Food and Drug Administration (US FDA) and the European Medicines Agency (EMA). In this chapter, we will discuss the array of natural and engineered immunoglobulins that are available as vectors for imaging and therapy as well as their in vivo modes of action. Several critical aspects of the accessibility and expression of targets related to the use of radioimmunoconjugates for imaging and therapy will be also discussed. These two introductory sections are followed by the core of the chapter in which we address the selection of appropriate radionuclide-immunoglobulin combinations, the possible applications of immunoPET and immunoSPECT, and how radiolabeled immunoglobulins can be evaluated.

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References

  1. Strebhardt K, Ullrich A. Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat Rev Cancer. 2008;8(6):473–80.

    Article  CAS  Google Scholar 

  2. Brekke OH, Sandlie I. Therapeutic antibodies for human diseases at the dawn of the twenty-first century. Nat Rev Drug Discov. 2003;2(1):52–62.

    Article  CAS  Google Scholar 

  3. Delves PJ, Martin SJ, Burton DR, Roitt IM. Roitt’s essential immunology. 13th ed. Chichester/Hoboken: John Wiley & Sons; 2017.

    Google Scholar 

  4. Vazquez-Lombardi R, Phan TG, Zimmermann C, Lowe D, Jermutu L, Christi D. Challenges and opportunities for non-antibody scaffold drugs. Drug Discov Today. 2015;20(10):1271–83.

    Article  CAS  Google Scholar 

  5. Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20(7):838–47.

    Article  CAS  Google Scholar 

  6. Liu LM. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. J Pharm Sci. 2015;104(6):1866–84.

    Article  CAS  Google Scholar 

  7. Weiner GJ. Building better monoclonal antibody-based therapeutics. Nat Rev Cancer. 2015;15(6):361–70.

    Article  CAS  Google Scholar 

  8. Reichert JM. Antibodies to watch in 2017. MAbs. 2017;9(2):167–81.

    Article  CAS  Google Scholar 

  9. Sehlin D, Fang XTT, Cato L, Antoni G, Lannfelt L, Syvanen S. Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer’s disease. Nat Commun. 2016;7:10759.

    Article  CAS  Google Scholar 

  10. Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87(5):586–92.

    Article  CAS  Google Scholar 

  11. Goldenberg DM. Targeted therapy of cancer with radiolabeled antibodies. J Nucl Med. 2002;43(5):693–713.

    CAS  PubMed  Google Scholar 

  12. Jain RK. Transport of molecules, particles and cells in solid tumors. Annu Rev Biomed Eng. 1999;1:241–63.

    Article  CAS  Google Scholar 

  13. Hillen F, Griffioen AW. Tumour vascularization: sprouting angiogenesis and beyond. Cancer Metastasis Rev. 2007;26(3–4):489–502.

    Article  Google Scholar 

  14. Wagner M, Wiig H. Tumor interstitial fluid formation, characterization, and clinical implications. Front Oncol. 2015;5:115.

    Article  Google Scholar 

  15. Olafsen T, Wu AM. Novel antibody vectors for imaging. Semin Nucl Med. 2010;40(3):167–81.

    Article  Google Scholar 

  16. Lamberts LE, Williams SP, Terwisscha van Scheltinga AG, Lub-de Hooge MN, Schroder CP, Gietema JA, et al. Antibody positron emission tomography imaging in anticancer drug development. J Clin Oncol. 2015;33(13):1491–504.

    Article  CAS  Google Scholar 

  17. Jauw YW, Menke-van der Houven van Oordt CW, Hoekstra OS, Hendrikse NH, Vugts DJ, Zijlstra JM, et al. Immuno-positron emission tomography with zirconium-89 labeled monoclonal antibodies in oncology: what can we learn from initial clinical trials? Front Pharmacol. 2016;7:131.

    Article  Google Scholar 

  18. Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32(1):40–51.

    Article  CAS  Google Scholar 

  19. Visser GW, Klok RP, Klein-Gebbink JW, Ter Linde T, Van Dongen GA, Molthoff CF. Optimal quality Iodine-131-monoclonal antibodies upon high dose labeling in a large reaction volume and temporarily coating the antibody with iodogen. J Nucl Med. 2001;42(3):509–19.

    CAS  PubMed  Google Scholar 

  20. Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA Jr. Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods. 1984;72(1):77–89.

    Article  CAS  Google Scholar 

  21. Van Gog FB, Rakenhoff RH, Snow GB, van Dongen GA. Rapid elimination of mouse/human chimeric monoclonal antibodies in nude mice. Cancer Immunol Immunother. 1997;44(2):103–11.

    Article  Google Scholar 

  22. Fleuren ED, Versleijen-Jonkers YM, Heskamp S, van Herpen CM, Oyen WJ, van der Graaf WT, Boerman OC. Theranostic applications of antibodies in oncology. Mol Oncol. 2014;8(4):799–812.

    Article  CAS  Google Scholar 

  23. Nayak TK, Brechbiel MW. Radioimmuno imaging with longer-lived positron-emitting radionuclides: potentials and challenges. Bioconjug Chem. 2009;20(5):825–41.

    Article  CAS  Google Scholar 

  24. Van Dongen GA, Poot AJ, Vugts DJ. PET imaging with radiolabeled antibodies and tyrosine kinase inhibitors: immuno-PET and TKI-PET. Tumor Biol. 2012;33(3):607–15.

    Article  CAS  Google Scholar 

  25. Bourgeois M, Bailly C, Frindel M, Guerard F, Cherel M, Faivre-Chauvet A, et al. Radioimmunoconjugates for treating cancer: recent advances and current opportunities. Expert Opin Biol Ther. 2017;17(7):813–9.

    Article  CAS  Google Scholar 

  26. Moek KL, Giesen D, Kok IC, de Groot DJA, Jalving M, Fehrmann RS, et al. Theranostics using antibodies and antibody-related therapeutics. J Nucl Med. 2017;58(Suppl 2):83S–90S.

    Article  CAS  Google Scholar 

  27. Knowles SM, Wu AM. Advances in immuno-positron emission tomography: antibodies for molecular imaging in oncology. J Clin Oncol. 2012;30(31):3884–92.

    Article  Google Scholar 

  28. Gaykema SB, Schröder CP, Vitfell-Rasmussen J, Chua S, Oude Munnink TH, Brouwers AH, et al. 89Zr-trastuzumab and 89Zr-bevacizumab PET to evaluate the effect of the HSP90 inhibitor NVP-AUY922 in metastatic breast cancer patients. Clin Cancer Res. 2014;20(15):3945–54.

    Article  CAS  Google Scholar 

  29. Arjaans M, Oude Munnink TH, Oosting SF, Terwisscha van Scheltinga AF, Gietema JA, Garbacik ET, et al. Bevacizumab-induced normalization of blood vessels in tumors hampers antibody uptake. Cancer Res. 2013;73(11):3347–55.

    Article  CAS  Google Scholar 

  30. Van der Veldt AA, Lubberink M, Bahce I, Walraven M, de Boer MP, Greuter HN, et al. Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling anti-angiogenic drugs. Cancer Cell. 2012;21(1):82–91.

    Article  Google Scholar 

  31. Van Asselt SJ, Oosting SF, Brouwers AH, Bongaerts AH, de Jong JR, Lub-de Hooge MN, et al. Everolimus reduces 89Zr-bevacizumab tumor uptake in patients with neuroendocrine tumors. J Nucl Med. 2014;55(7):1087–92.

    Article  Google Scholar 

  32. Gebhart G, Lamberts LE, Wimana Z, Garcia C, Emonts P, Ameye L, et al. Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial. Ann Oncol. 2017;27(4):619–24.

    Article  Google Scholar 

  33. Jauw YW, Huisman MC, Nayak TK, Vugts DJ, Christen R, Naegelen VM, et al. Assessment of target-mediated uptake with immuno-PET: analysis of a phase I clinical trial with an anti-CD44 antibody. EJNMMI Res. 2018;8(1):6.

    Article  Google Scholar 

  34. Freise A, Wu AM. In vivo imaging with antibodies and engineered fragments. Mol Immunol. 2015;67(2 Pt A):142–52.

    Article  CAS  Google Scholar 

  35. Wu A. Engineered antibodies for molecular imaging of cancer. Methods. 2014;65(1):139–47.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

    Danielle J. Vugts & Guus A. M. S. van Dongen

Authors
  1. Danielle J. Vugts
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  2. Guus A. M. S. van Dongen
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Correspondence to Danielle J. Vugts .

Editor information

Editors and Affiliations

  1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jason S. Lewis

  2. Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

    Albert D. Windhorst

  3. Department of Chemistry, Hunter College, City University of New York, New York, NY, USA

    Brian M. Zeglis

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Vugts, D.J., van Dongen, G.A.M.S. (2019). Immunoglobulins as Radiopharmaceutical Vectors. In: Lewis, J., Windhorst, A., Zeglis, B. (eds) Radiopharmaceutical Chemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-98947-1_9

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  • DOI: https://doi.org/10.1007/978-3-319-98947-1_9

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-98946-4

  • Online ISBN: 978-3-319-98947-1

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