A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer.
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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.
SubjectScience & Technology
Science & Technology - Other Topics
NONSMALL CELL LUNG
Published Version (Please cite this version)10.1371/journal.pone.0206950
Publication InfoAshton, Jeffrey R; Gottlin, Elizabeth B; Patz, Edward F; West, Jennifer L; & Badea, Cristian T (2018). A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer. PloS one, 13(11). pp. e0206950. 10.1371/journal.pone.0206950. Retrieved from https://hdl.handle.net/10161/18055.
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Professor in Radiology
Dr. Cristian T. Badea is a Professor in the Department of Radiology and faculty in the Departments of Biomedical Engineering and Medical Physics. His research interests are in the physics and biomedical applications of computed tomography (CT), micro-CT, tomosynthesis, and image reconstruction algorithms.
Assistant Professor in Radiology
James and Alice Chen Distinguished Professor of Radiology
There are numerous ongoing clinical studies primarily focused on the early detection of cancer. The basic science investigations in our laboratory concentration on three fundamental translational areas, 1) Development of molecular imaging probes - We have used several different approaches to develop novel imaging probes that characterize and phenotype tumors. 2) Discovery of novel lung cancer biomarkers - We ex
Fitzpatrick Family University Distinguished Professor of Engineering
Jennifer West’s research in biomaterials and tissue engineering involves the synthesis, development, and application of novel, biofunctional materials, and the use of biomaterials and engineering approaches to study biological problems. Current projects include the design of ECM-mimetic hydrogel materials, novel microfabrication strategies for biomimetic patterning, and nanoparticle theranostics.
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