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.

Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones

“…Alternatively, other study demonstrated the feasibility of gold nanoparticle functionalization and resulting biological impact in terms of selective recognition [194,195]. Given the possibility of doping the GNP with radionuclides [196], or to use gold as a means to influence dose deposition [197,198], gold nanoparticle functionalization may represent an opportune tool for GBM targeting and therapy that remains to be evaluated. Other strategies for radiosensitization by use of nanomedicines can include vectorization of endostatin [199], curcumin [200][201][202][203], TMZ [204], and action on NF-kB [205].…”

Radiolabeled Nanoparticles in Nuclear Oncology

“…The team used a new method for the synthesis, compared the biodistribution before and after the coupling reaction and evaluated quantitive PET imaging performance of the complexes. In vitro studies showed that all conjugates were stable, while in vivo distribution showed no alteration in tumor uptake between the conjugated and unconjugated cetuximab, indicating that 89 Zr-labeled cetuximab-targeted nanoparticles preserved their tumor targeting properties [34]. Ultra-small paramagnetic iron oxide nanoparticles (USPIOs) were developed to create stable and chelate-free radiolabeled complexes using a novel reaction process.…”

Gold nanoparticles for cancer theranostics — A brief update

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