title: Antibody-functionalized nanoparticles for imaging cancer: influence of conjugation to gold nanoparticles on the biodistribution of 89Zr-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.
authors.affiliation: Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue Mounier 73, 1200, Brussels, Belgium.
authors.forename: Linda
authors.initials: L
authors.lastname: Karmani
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.forename: Vanessa
authors.initials: V
authors.lastname: Valembois
authors.forename: Virginie
authors.initials: V
authors.lastname: Bouchat
authors.forename: Praveen Ganesh
authors.initials: PG
authors.lastname: Nagaswaran
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.forename: Jacques
authors.initials: J
authors.lastname: Gillart
authors.forename: Philippe
authors.initials: P
authors.lastname: Levêque
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.forename: Davide
authors.initials: D
authors.lastname: Bonifazi
authors.forename: Carine
authors.initials: C
authors.lastname: Michiels
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lucas
authors.forename: Thierry
authors.initials: T
authors.lastname: Vander Borght
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D000068818:Cetuximab; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D057054:Molecular Imaging; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D011859:Radiography; D011868:Radioisotopes / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays; D015040:Zirconium / Q000008:administration & dosage
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D011868:Radioisotopes; D006046:Gold; D015040:Zirconium; D000068818:Cetuximab