Skip to main content

Molecular Imaging Using Nanobodies: A Case Study

  • Protocol
  • First Online:
Single Domain Antibodies

Abstract

Molecular imaging is a noninvasive method to measure specific biological processes in animal models and patients using imaging. In recent years there has been a tremendous evolution in hardware and software for imaging purposes. This progress has created an urgent need for new labeled targeted molecular probes. The unique physicochemical and pharmacokinetic properties of Nanobodies match the requirements of the ideal molecular imaging tracer. Preclinical studies show strong and specific targeting in vivo with rapid clearance of unbound probe resulting in high contrasted images at early time points after intravenous administration. These data suggest that the Nanobody platform might become a generic method for the development of next generation molecular imaging probes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pysz MA, Gambhir SS, Willmann JK (2010) Molecular imaging: current status and emerging strategies. Clin Radiol 65:500–516

    Article  PubMed  CAS  Google Scholar 

  2. Gainkam LO, Huang L, Caveliers V et al (2008) Comparison of the biodistribution and tumor targeting of two 99mTc-labeled anti-EGFR nanobodies in mice, using pinhole SPECT/micro-CT. J Nucl Med 49:788–795

    Article  PubMed  CAS  Google Scholar 

  3. Vaneycken I, Devoogdt N, Van Gamer N, Vincke C, Xavier C, Nennery U, Muyldermans S, Lahoutte T, Caveliers V (2011) Pre-clinical screening of anti-HER2 Nanobodies for molecular imaging of breast cancer. FASEB J 25: 2433–2446

    Google Scholar 

  4. Van Bockstaele F, Holz JB, Revets H (2009) The development of nanobodies for therapeutic applications. Curr Opin Investig Drugs 10:1212–1224

    PubMed  Google Scholar 

  5. Hmila I, Saerens D, Ben Abderrazek R, Vincke C, Abidi N, Benlasfar Z, Govaert J, El Ayeb M, Bouhaouala-Zahar B, Muyldermans S (2010) A bispecific nanobody to provide full protection against lethal scorpion envenoming. FASEB J 24:3479–3489

    Article  PubMed  CAS  Google Scholar 

  6. Ulrichts H, Silence K, Schoolmeester A, de Jaegere P, Rossenu S, Roodt J, Priem S, Lauwereys M, Casteels P, Van Bockstaele F, Verschueren K, Stanssens P, Baumeister J, Holz JB (2011) Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared to currently marketed antiplatelet drugs. Blood 118:757–765

    Article  PubMed  CAS  Google Scholar 

  7. Van de Broek B, Devoogdt N, D’Hollander A, Gijs HL, Jans K, Lagae L, Muyldermans S, Maes G, Borghs G (2011) Specific cell targeting with nanobody conjugated branched gold nanoparticles for photothermal therapy. ACS Nano 5:4319–4328

    Article  PubMed  Google Scholar 

  8. Roovers RC, Laeremans T, Huang L, De Taeye S, Verkleij AJ, Revets H, de Haard HJ, Van Bergen en Henegouwen PM (2007) Efficient inhibition of EGFR signaling and of tumour growth by antagonistic anti-EFGR Nanobodies. Cancer Immunol Immunother 56:303–317

    Article  PubMed  CAS  Google Scholar 

  9. Conrath K, Lauwereys M, Wyns L, Muyldermans S (2001) Camel single-domain antibodies as modular building units in bispecific and bivalent antibody constructs. J Biol Chem 276:7346–7350

    Article  CAS  Google Scholar 

  10. Hmila I, Abdallah RB, Saerens D, Benlasfar Z, Conrath K, Ayeb ME, Muyldermans S, Bouhaouala-Zahar B (2008) VHH, bivalent domains and chimeric Heavy chain-only antibodies with high neutralizing efficacy for scorpion toxin AahI’. Mol Immunol 45:3847–3856

    Article  PubMed  CAS  Google Scholar 

  11. Tijink BM, Laeremans T, Budde M, Stigter-van Walsum M, Dreier T, de Haard HJ, Leemans CR, van Dongen GA (2008) Improved tumor targeting of anti-epidermal growth factor receptor Nanobodies through albumin binding: taking advantage of modular Nanobody technology. Mol Cancer Ther 7:2288–2297

    Article  PubMed  CAS  Google Scholar 

  12. Waibel R, Alberto R, Willuda J, Finnern R, Schibli R, Stichelberger A, Egli A, Abram U, Mach JP, Pluckthun A, Schubiger PA (1999) Stable one-step technetium-99 m labeling of His-tagged recombinant proteins with a novel Tc(I)-carbonyl complex. Nat Biotechnol 17:897–901

    Article  PubMed  CAS  Google Scholar 

  13. Vaneycken I, Govaert J, Vincke C, Caveliers V, Lahoutte T, De Baetselier P, Raes G, Bossuyt A, Muyldermans S, Devoogdt N (2010) In vitro analysis and in vivo tumor targeting of a humanized, grafted nanobody in mice using pinhole SPECT/micro-CT. J Nucl Med 51:1099–1106

    Article  PubMed  CAS  Google Scholar 

  14. Huang L, Gainkam LO, Caveliers V, Vanhove C, Keyaerts M, De Baetselier P, Bossuyt A, Revets H, Lahoutte T (2008) SPECT imaging with 99mTc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression. Mol Imaging Biol 10:167–175

    Article  PubMed  Google Scholar 

  15. Vincke C, Loris R, Saerens D, Martinez-Rodriguez S, Muyldermans S, Conrath K (2009) General strategy to humanize a camelid single-domain antibody and identification of a universal humanized nanobody scaffold. J Biol Chem 284:3273–3284

    Article  PubMed  CAS  Google Scholar 

  16. Weissleder R, Ntziachristos V (2003) Shedding light onto live molecular targets. Nat Med 9:123–128

    Article  PubMed  CAS  Google Scholar 

  17. Gainkam LO, Caveliers V, Devoogdt N, Vanhove C, Xavier C, Boerman O, Muyldermans S, Bossuyt A, Lahoutte T (2011) Localization, mechanism and reduction of renal retention of technetium-99 m labeled epidermal growth factor receptor-specific nanobody in mice. Contrast Media Mol Imaging 6:85–92

    Article  PubMed  Google Scholar 

  18. Cortez-Retamozo V, Lahoutte T, Caveliers V, Tchouate-Gainkam O, Hernot S, Packeu A, De Vos F, Vanhove C, Muyldermans S, De Baetselier P, Revets H (2008) 99mTc-labeled nanobodies: a new type of targeted probes for imaging antigen expression. Curr Radiopharm 1:37–41

    CAS  Google Scholar 

  19. Tchouate LO, Gainkam M, Keyaerts V, Caveliers N, Devoogdt C, Vanhove LV, Grunsven SM, Lahoutte T (2011) Correlation between epidermal growth factor receptor-specific nanobody uptake and tumor burden: a tool for noninvasive monitoring of tumor response to therapy. Mol Imaging Biol 13(5):940–948

    Article  Google Scholar 

  20. De Groeve K, Deschacht N, De Koninck C, Caveliers V, Lahoutte T, Devoogdt N, Muyldermans S, De Baetselier P, Raes G (2010) Nanobodies as tools for in vivo imaging of specific immune cell types. J Nucl Med 51:782–789

    Article  PubMed  Google Scholar 

  21. Dijkers EC, Kosterink JG, Rademaker AP, Perk LR, van Dongen GA, Bart J, de Jong JR, de Vries EG, Lub-de Hooge MN (2009) Development and characterization of clinical-grade 89Zr-trastuzumab for HER2/neu immunoPET imaging. J Nucl Med 50:974–981

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tony Lahoutte .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Devoogdt, N. et al. (2012). Molecular Imaging Using Nanobodies: A Case Study. In: Saerens, D., Muyldermans, S. (eds) Single Domain Antibodies. Methods in Molecular Biology, vol 911. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-968-6_35

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-968-6_35

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-967-9

  • Online ISBN: 978-1-61779-968-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics