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A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer.

Publication ,  Journal Article
Ashton, JR; Gottlin, EB; Patz, EF; West, JL; Badea, CT
Published in: PLoS One
2018

Computed tomography (CT) is the standard imaging test used for the screening and assessment of suspected lung cancer, but distinguishing malignant from benign nodules by CT is an ongoing challenge. Consequently, a large number of avoidable invasive procedures are performed on patients with benign nodules in order to exclude malignancy. Improving cancer discrimination by non-invasive imaging could reduce the need for invasive diagnostics. In this work we focus on developing a gold nanoparticle contrast agent that targets the epidermal growth factor receptor (EGFR), which is expressed on the cell surface of most lung adenocarcinomas. Three different contrast agents were compared for their tumor targeting effectiveness: non-targeted nanoparticles, nanoparticles conjugated with full-sized anti-EGFR antibodies (cetuximab), and nanoparticles conjugated with a single-domain llama-derived anti-EGFR antibody, which is smaller than the cetuximab, but has a lower binding affinity. Nanoparticle targeting effectiveness was evaluated in vitro by EGFR-binding assays and in cell culture with A431 cells, which highly express EGFR. In vivo CT imaging performance was evaluated in both C57BL/6 mice and in nude mice with A431 subcutaneous tumors. The cetuximab nanoparticles had a significantly shorter blood residence time than either the non-targeted or the single-domain antibody nanoparticles. All of the nanoparticle contrast agents demonstrated tumor accumulation; however, the cetuximab-targeted group had significantly higher tumor gold accumulation than the other two groups, which were statistically indistinguishable from one another. In this study we found that the relative binding affinity of the targeting ligands had more of an effect on tumor accumulation than the circulation half life of the nanoparticles. This study provides useful insight into targeted nanoparticle design and demonstrates that nanoparticle contrast agents can be used to detect tumor receptor overexpression. Combining receptor status data with traditional imaging characteristics has the potential for better differentiation of malignant lung tumors from benign lesions.

Duke Scholars

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2018

Volume

13

Issue

11

Start / End Page

e0206950

Location

United States

Related Subject Headings

  • X-Ray Microtomography
  • Transplantation, Heterologous
  • Tissue Distribution
  • Single-Domain Antibodies
  • Mice, Nude
  • Mice, Inbred C57BL
  • Mice
  • Metal Nanoparticles
  • Lung Neoplasms
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ashton, J. R., Gottlin, E. B., Patz, E. F., West, J. L., & Badea, C. T. (2018). A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer. PLoS One, 13(11), e0206950. https://doi.org/10.1371/journal.pone.0206950
Ashton, Jeffrey R., Elizabeth B. Gottlin, Edward F. Patz, Jennifer L. West, and Cristian T. Badea. “A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer.PLoS One 13, no. 11 (2018): e0206950. https://doi.org/10.1371/journal.pone.0206950.
Ashton JR, Gottlin EB, Patz EF, West JL, Badea CT. A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer. PLoS One. 2018;13(11):e0206950.
Ashton, Jeffrey R., et al. “A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer.PLoS One, vol. 13, no. 11, 2018, p. e0206950. Pubmed, doi:10.1371/journal.pone.0206950.
Ashton JR, Gottlin EB, Patz EF, West JL, Badea CT. A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer. PLoS One. 2018;13(11):e0206950.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2018

Volume

13

Issue

11

Start / End Page

e0206950

Location

United States

Related Subject Headings

  • X-Ray Microtomography
  • Transplantation, Heterologous
  • Tissue Distribution
  • Single-Domain Antibodies
  • Mice, Nude
  • Mice, Inbred C57BL
  • Mice
  • Metal Nanoparticles
  • Lung Neoplasms
  • Humans