Startseite Radiometal-labeled anti-VCAM-1 nanobodies as molecular tracers for atherosclerosis – impact of radiochemistry on pharmacokinetics
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Radiometal-labeled anti-VCAM-1 nanobodies as molecular tracers for atherosclerosis – impact of radiochemistry on pharmacokinetics

  • Gezim Bala , Maxine Crauwels , Anneleen Blykers , Isabel Remory , Andrea L.J. Marschall , Stefan Dübel , Laurent Dumas , Alexis Broisat , Charlotte Martin , Steven Ballet , Bernard Cosyns , Vicky Caveliers , Nick Devoogdt , Catarina Xavier und Sophie Hernot ORCID logo EMAIL logo
Veröffentlicht/Copyright: 21. September 2018
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 400 Heft 3

Abstract

Radiolabeling of nanobodies with radiometals by chelation has the advantage of being simple, fast and easy to implement in clinical routine. In this study, we validated 68Ga/111In-labeled anti-VCAM-1 nanobodies as potential radiometal-based tracers for molecular imaging of atherosclerosis. Both showed specific targeting of atherosclerotic lesions in ApoE−/− mice. Nevertheless, uptake in lesions and constitutively VCAM-1 expressing organs was lower than previously reported for the 99mTc-labeled analog. We further investigated the impact of different radiolabeling strategies on the in vivo biodistribution of nanobody-based tracers. Comparison of the pharmacokinetics between 68Ga-, 18F-, 111In- and 99mTc-labeled anti-VCAM-1 nanobodies showed highest specific uptake for 99mTc-nanobody at all time-points, followed by the 68Ga-, 111In- and 18F-labeled tracer. No correlation was found with the estimated number of radioisotopes per nanobody, and mimicking specific activity of other radiolabeling methods did not result in an analogous biodistribution. We also demonstrated specificity of the tracer using mice with a VCAM-1 knocked-down phenotype, while showing for the first time the in vivo visualization of a protein knock-down using intrabodies. Conclusively, the chosen radiochemistry does have an important impact on the biodistribution of nanobodies, in particular on the specific targeting, but differences are not purely due to the tracer’s specific activity.

Keywords: mass effect; molecular imaging; single-domain antibody fragment; specific activity; VCAM-1 knock-down mice; vulnerable plaque

Acknowledgments

This work was supported by the Research Foundation-Flanders, Belgium, Funder Id: 10.13039/501100003130 (FWO G066615N and G005815N), the Strategic Research Program-Growth funding of the Vrije Universiteit Brussel (VUB) and the Wetenschappelijk Fonds Willy Gepts. We thank Cindy Peleman and Jan De Jonge for their technical assistance.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0330).

Received: 2018-07-30
Accepted: 2018-08-20
Published Online: 2018-09-21
Published in Print: 2019-02-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Protein engineering comes of age
  3. Microbial transglutaminase for biotechnological and biomedical engineering
  4. Computational design of structured loops for new protein functions
  5. Formylglycine-generating enzymes for site-specific bioconjugation
  6. Chemical modification of neuropeptide Y for human Y1 receptor targeting in health and disease
  7. Manipulating the stereoselectivity of a thermostable alcohol dehydrogenase by directed evolution for efficient asymmetric synthesis of arylpropanols
  8. Radiometal-labeled anti-VCAM-1 nanobodies as molecular tracers for atherosclerosis – impact of radiochemistry on pharmacokinetics
  9. Hit evaluation of an α-helical peptide: Ala-scan, truncation and sidechain-to-sidechain macrocyclization of an RNA polymerase Inhibitor
  10. Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing
  11. An engineered lipocalin that tightly complexes the plant poison colchicine for use as antidote and in bioanalytical applications
  12. Sequence selection by FitSS4ASR alleviates ancestral sequence reconstruction as exemplified for geranylgeranylglyceryl phosphate synthase
  13. Facile generation of antibody heavy and light chain diversities for yeast surface display by Golden Gate Cloning
  14. Peptide binding affinity redistributes preassembled repeat protein fragments
  15. Directed evolution of the 3C protease from coxsackievirus using a novel fluorescence-assisted intracellular method
  16. Rational design of an improved photo-activatable intein for the production of head-to-tail cyclized peptides
  17. Characterization and engineering of photoactivated adenylyl cyclases
https://doi.org/10.1515/hsz-2018-0330
Schlagwörter für diesen Artikel
mass effect; molecular imaging; single-domain antibody fragment; specific activity; VCAM-1 knock-down mice; vulnerable plaque

Artikel in diesem Heft

  1. Frontmatter
  2. Protein engineering comes of age
  3. Microbial transglutaminase for biotechnological and biomedical engineering
  4. Computational design of structured loops for new protein functions
  5. Formylglycine-generating enzymes for site-specific bioconjugation
  6. Chemical modification of neuropeptide Y for human Y1 receptor targeting in health and disease
  7. Manipulating the stereoselectivity of a thermostable alcohol dehydrogenase by directed evolution for efficient asymmetric synthesis of arylpropanols
  8. Radiometal-labeled anti-VCAM-1 nanobodies as molecular tracers for atherosclerosis – impact of radiochemistry on pharmacokinetics
  9. Hit evaluation of an α-helical peptide: Ala-scan, truncation and sidechain-to-sidechain macrocyclization of an RNA polymerase Inhibitor
  10. Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing
  11. An engineered lipocalin that tightly complexes the plant poison colchicine for use as antidote and in bioanalytical applications
  12. Sequence selection by FitSS4ASR alleviates ancestral sequence reconstruction as exemplified for geranylgeranylglyceryl phosphate synthase
  13. Facile generation of antibody heavy and light chain diversities for yeast surface display by Golden Gate Cloning
  14. Peptide binding affinity redistributes preassembled repeat protein fragments
  15. Directed evolution of the 3C protease from coxsackievirus using a novel fluorescence-assisted intracellular method
  16. Rational design of an improved photo-activatable intein for the production of head-to-tail cyclized peptides
  17. Characterization and engineering of photoactivated adenylyl cyclases
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