Antibody-functionalized nanoparticles for imaging cancer influence of conjugation to gold nanoparticles on the biodistribution of (89) Zr-labeled cetuximab in mice

Linda Karmani, Daniel Labar, Vanessa Valembois, Virginie Bouchat, Praveen Ganesh Nagaswaran, Anne Bol, Jacques Gillart, Philippe Levêque, Caroline Bouzin, Davide Bonifazi, Carine Michiels, Olivier Feron, Vincent Grégoire, Stéphane Lucas, Thierry Vander Borght, Bernard Gallez

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Antibody-labeled gold nanoparticles represent a promising novel tool regarding cancer imaging and therapy. Nevertheless, the characterization of biodistribution of such immunonanocarriers has been poorly documented. In this study, the biodistribution of (89) Zr-labeled cetuximab before and after the coupling reaction to gold nanoparticles (AuNPs) was compared and the quantitative imaging performance of (89) Zr immuno-PET was evaluated. Cetuximab was functionalized with the desferal moiety and labeled with (89) Zr ((89) Zr-Df-Bz-NCS-cetuximab). AuNPs with a mean diameter of 5 nm were synthesized according a new method developed in the laboratory, and conjugated to (89) Zr-Df-Bz-NCS-cetuximab using carbodiimide chemistry (AuNPs-PPAA-cetuximab-(89) Zr). The two tracers were injected in A431 xenograft-bearing mice. Tumor and liver uptakes were assessed at different times after injection using quantitative PET imaging. The in vivo specificity of the binding was investigated using a saturating dose of unlabeled cetuximab. Radiolabeled cetuximab was conjugated to AuNPs with a coupling reaction yield >75%. All conjugates were stable in vitro and to a lesser extent in plasma. In vivo distribution studies revealed no significant difference in tumor uptake for cetuximab conjugated to nanoparticles up to 72 h after injection, compared with unconjugated cetuximab. Immuno-PET studies showed that AuNPs-PPAA-cetuximab-(89) Zr provided high tumor-to-background ratio. The liver uptake of AuNPs-PPAA-cetuximab-(89) Zr was higher, compared with (89) Zr-Df-Bz-NCS-cetuximab. In vivo blocking experiments demonstrated selective tumor targeting after coupling reaction. This study showed that the conjugation of AuNPs to cetuximab did not affect its tumor accumulation and that the efficacy of EGFR-targeted nanoparticles was unaltered. The (89) Zr-labeled cetuximab-targeted gold nanoparticles could be a valuable tool for theranostic purposes. Copyright © 2013 John Wiley & Sons, Ltd.
langue originaleAnglais
Pages (de - à)402-8
Nombre de pages7
journalContrast Media and Molecular Imaging
Volume8
Numéro de publication5
Les DOIs
étatPublié - 2013

Empreinte digitale

Gold
Nanoparticles
Antibodies
Neoplasms
Cetuximab
Carbodiimides
Injections
Deferoxamine
Liver
Heterografts

Citer ceci

Karmani, Linda ; Labar, Daniel ; Valembois, Vanessa ; Bouchat, Virginie ; Nagaswaran, Praveen Ganesh ; Bol, Anne ; Gillart, Jacques ; Levêque, Philippe ; Bouzin, Caroline ; Bonifazi, Davide ; Michiels, Carine ; Feron, Olivier ; Grégoire, Vincent ; Lucas, Stéphane ; Borght, Thierry Vander ; Gallez, Bernard. / Antibody-functionalized nanoparticles for imaging cancer influence of conjugation to gold nanoparticles on the biodistribution of (89) Zr-labeled cetuximab in mice. Dans: Contrast Media and Molecular Imaging. 2013 ; Vol 8, Numéro 5. p. 402-8.
@article{2a102b4d794f4be48f5204da0621d12f,
title = "Antibody-functionalized nanoparticles for imaging cancer influence of conjugation to gold nanoparticles on the biodistribution of (89) Zr-labeled cetuximab in mice",
abstract = "Antibody-labeled gold nanoparticles represent a promising novel tool regarding cancer imaging and therapy. Nevertheless, the characterization of biodistribution of such immunonanocarriers has been poorly documented. In this study, the biodistribution of (89) Zr-labeled cetuximab before and after the coupling reaction to gold nanoparticles (AuNPs) was compared and the quantitative imaging performance of (89) Zr immuno-PET was evaluated. Cetuximab was functionalized with the desferal moiety and labeled with (89) Zr ((89) Zr-Df-Bz-NCS-cetuximab). AuNPs with a mean diameter of 5 nm were synthesized according a new method developed in the laboratory, and conjugated to (89) Zr-Df-Bz-NCS-cetuximab using carbodiimide chemistry (AuNPs-PPAA-cetuximab-(89) Zr). The two tracers were injected in A431 xenograft-bearing mice. Tumor and liver uptakes were assessed at different times after injection using quantitative PET imaging. The in vivo specificity of the binding was investigated using a saturating dose of unlabeled cetuximab. Radiolabeled cetuximab was conjugated to AuNPs with a coupling reaction yield >75{\%}. All conjugates were stable in vitro and to a lesser extent in plasma. In vivo distribution studies revealed no significant difference in tumor uptake for cetuximab conjugated to nanoparticles up to 72 h after injection, compared with unconjugated cetuximab. Immuno-PET studies showed that AuNPs-PPAA-cetuximab-(89) Zr provided high tumor-to-background ratio. The liver uptake of AuNPs-PPAA-cetuximab-(89) Zr was higher, compared with (89) Zr-Df-Bz-NCS-cetuximab. In vivo blocking experiments demonstrated selective tumor targeting after coupling reaction. This study showed that the conjugation of AuNPs to cetuximab did not affect its tumor accumulation and that the efficacy of EGFR-targeted nanoparticles was unaltered. The (89) Zr-labeled cetuximab-targeted gold nanoparticles could be a valuable tool for theranostic purposes. Copyright {\circledC} 2013 John Wiley & Sons, Ltd.",
author = "Linda Karmani and Daniel Labar and Vanessa Valembois and Virginie Bouchat and Nagaswaran, {Praveen Ganesh} and Anne Bol and Jacques Gillart and Philippe Lev{\^e}que and Caroline Bouzin and Davide Bonifazi and Carine Michiels and Olivier Feron and Vincent Gr{\'e}goire and St{\'e}phane Lucas and Borght, {Thierry Vander} and Bernard Gallez",
note = "Copyright {\circledC} 2013 John Wiley & Sons, Ltd.",
year = "2013",
doi = "10.1002/cmmi.1539",
language = "English",
volume = "8",
pages = "402--8",
journal = "Contrast Media and Molecular Imaging",
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Antibody-functionalized nanoparticles for imaging cancer influence of conjugation to gold nanoparticles on the biodistribution of (89) Zr-labeled cetuximab in mice. / Karmani, Linda; Labar, Daniel; Valembois, Vanessa; Bouchat, Virginie; Nagaswaran, Praveen Ganesh; Bol, Anne; Gillart, Jacques; Levêque, Philippe; Bouzin, Caroline; Bonifazi, Davide; Michiels, Carine; Feron, Olivier; Grégoire, Vincent; Lucas, Stéphane; Borght, Thierry Vander; Gallez, Bernard.

Dans: Contrast Media and Molecular Imaging, Vol 8, Numéro 5, 2013, p. 402-8.

Résultats de recherche: Contribution à un journal/une revueArticle

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T1 - Antibody-functionalized nanoparticles for imaging cancer influence of conjugation to gold nanoparticles on the biodistribution of (89) Zr-labeled cetuximab in mice

AU - Karmani, Linda

AU - Labar, Daniel

AU - Valembois, Vanessa

AU - Bouchat, Virginie

AU - Nagaswaran, Praveen Ganesh

AU - Bol, Anne

AU - Gillart, Jacques

AU - Levêque, Philippe

AU - Bouzin, Caroline

AU - Bonifazi, Davide

AU - Michiels, Carine

AU - Feron, Olivier

AU - Grégoire, Vincent

AU - Lucas, Stéphane

AU - Borght, Thierry Vander

AU - Gallez, Bernard

N1 - Copyright © 2013 John Wiley & Sons, Ltd.

PY - 2013

Y1 - 2013

N2 - Antibody-labeled gold nanoparticles represent a promising novel tool regarding cancer imaging and therapy. Nevertheless, the characterization of biodistribution of such immunonanocarriers has been poorly documented. In this study, the biodistribution of (89) Zr-labeled cetuximab before and after the coupling reaction to gold nanoparticles (AuNPs) was compared and the quantitative imaging performance of (89) Zr immuno-PET was evaluated. Cetuximab was functionalized with the desferal moiety and labeled with (89) Zr ((89) Zr-Df-Bz-NCS-cetuximab). AuNPs with a mean diameter of 5 nm were synthesized according a new method developed in the laboratory, and conjugated to (89) Zr-Df-Bz-NCS-cetuximab using carbodiimide chemistry (AuNPs-PPAA-cetuximab-(89) Zr). The two tracers were injected in A431 xenograft-bearing mice. Tumor and liver uptakes were assessed at different times after injection using quantitative PET imaging. The in vivo specificity of the binding was investigated using a saturating dose of unlabeled cetuximab. Radiolabeled cetuximab was conjugated to AuNPs with a coupling reaction yield >75%. All conjugates were stable in vitro and to a lesser extent in plasma. In vivo distribution studies revealed no significant difference in tumor uptake for cetuximab conjugated to nanoparticles up to 72 h after injection, compared with unconjugated cetuximab. Immuno-PET studies showed that AuNPs-PPAA-cetuximab-(89) Zr provided high tumor-to-background ratio. The liver uptake of AuNPs-PPAA-cetuximab-(89) Zr was higher, compared with (89) Zr-Df-Bz-NCS-cetuximab. In vivo blocking experiments demonstrated selective tumor targeting after coupling reaction. This study showed that the conjugation of AuNPs to cetuximab did not affect its tumor accumulation and that the efficacy of EGFR-targeted nanoparticles was unaltered. The (89) Zr-labeled cetuximab-targeted gold nanoparticles could be a valuable tool for theranostic purposes. Copyright © 2013 John Wiley & Sons, Ltd.

AB - Antibody-labeled gold nanoparticles represent a promising novel tool regarding cancer imaging and therapy. Nevertheless, the characterization of biodistribution of such immunonanocarriers has been poorly documented. In this study, the biodistribution of (89) Zr-labeled cetuximab before and after the coupling reaction to gold nanoparticles (AuNPs) was compared and the quantitative imaging performance of (89) Zr immuno-PET was evaluated. Cetuximab was functionalized with the desferal moiety and labeled with (89) Zr ((89) Zr-Df-Bz-NCS-cetuximab). AuNPs with a mean diameter of 5 nm were synthesized according a new method developed in the laboratory, and conjugated to (89) Zr-Df-Bz-NCS-cetuximab using carbodiimide chemistry (AuNPs-PPAA-cetuximab-(89) Zr). The two tracers were injected in A431 xenograft-bearing mice. Tumor and liver uptakes were assessed at different times after injection using quantitative PET imaging. The in vivo specificity of the binding was investigated using a saturating dose of unlabeled cetuximab. Radiolabeled cetuximab was conjugated to AuNPs with a coupling reaction yield >75%. All conjugates were stable in vitro and to a lesser extent in plasma. In vivo distribution studies revealed no significant difference in tumor uptake for cetuximab conjugated to nanoparticles up to 72 h after injection, compared with unconjugated cetuximab. Immuno-PET studies showed that AuNPs-PPAA-cetuximab-(89) Zr provided high tumor-to-background ratio. The liver uptake of AuNPs-PPAA-cetuximab-(89) Zr was higher, compared with (89) Zr-Df-Bz-NCS-cetuximab. In vivo blocking experiments demonstrated selective tumor targeting after coupling reaction. This study showed that the conjugation of AuNPs to cetuximab did not affect its tumor accumulation and that the efficacy of EGFR-targeted nanoparticles was unaltered. The (89) Zr-labeled cetuximab-targeted gold nanoparticles could be a valuable tool for theranostic purposes. Copyright © 2013 John Wiley & Sons, Ltd.

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JO - Contrast Media and Molecular Imaging

JF - Contrast Media and Molecular Imaging

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