Epidermal growth factor receptor targeting using cetuximab labeledultrasound contrast agents A feasibility study

Joseph Knowles, Hope Heath, Reshu Saini, Heidi Umphrey, Eben Rosenthal, Kenneth Hoyt

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Citation (Scopus)

Abstract

This paper details the potential of cetuximab (C225) labeled microbubbles(MBs) to improve ultrasound (US) imaging of head and neck squamous cellcarcinoma (HNSCC). C225 is a therapeutic monoclonal antibody to the epidermalgrowth factor receptor (EGFR) and currently approved for the treatment ofrecurrent HNSCC. Conjugating C225 to the surface of US MBs produces a targetedcontrast agent that selectively binds to over-expressed EGFR on the tumorendothelium to improve visualization and therapeutic monitoring. Analysis oftargeted MB binding in vitro was performed using SCC-1 and normal dermalfibroblasts (NDF) cell lines. Cells were incubated with MBs conjugated to eitherC225 or IgG isotype control antibodies. Light microscopy was used to quantifyMB receptor binding. Attached MB were normalized by cell count and recorded foreach group. To evaluate C225-labeled MBs in an animal model, SCC-1 cells wereimplanted in the flank of nude athymic mice (N=8). MBs labeled with C225 orcontrol antibodies were administered via a bolus tail vein injection and tumorswere examined using a MB sensitive harmonic imaging mode. For each tumor, USimages from the targeted and control groups were paired and assessed by ablinded reviewer to determine greatest degree of intratumoral contrastenhancement. MBs labeled with C225 exhibited significantly higher SCC-1 cellattachment levels relative to control group measurements (p=0.001).Specifically, the mean number of attached MBs per cell was 3.6±0.7 and0.7±0.1 for the C225-and control antibody-labeled groups, respectively,yielding nearly a 6-fold difference. Given presentation of paired animal data,it was determined that 75% (6 of 8) of the US images from the C225-labeled MBexperimental day exhibited increased enhancement compared to the same animalsadministered control MBs. This study demonstrates feasibility of targeted USimaging of HNSCC using cetuximab-labeled MBs.

Original languageEnglish (US)
Title of host publication2010 IEEE International Ultrasonics Symposium, IUS 2010
Pages1593-1595
Number of pages3
DOIs
StatePublished - Dec 1 2010
Event2010 IEEE International Ultrasonics Symposium, IUS 2010 - San Diego, CA, United States
Duration: Oct 11 2010Oct 14 2010

Other

Other2010 IEEE International Ultrasonics Symposium, IUS 2010
CountryUnited States
CitySan Diego, CA
Period10/11/1010/14/10

Fingerprint

antibodies
cells
animal models
veins
cultured cells
mice
animals
tumors
injection
microscopy
harmonics
augmentation

Keywords

  • Cetuximab
  • head and neck squamous cell carcinoma
  • microbubbles
  • molecular imaging
  • ultrasound

ASJC Scopus subject areas

  • Acoustics and Ultrasonics

Cite this

Knowles, J., Heath, H., Saini, R., Umphrey, H., Rosenthal, E., & Hoyt, K. (2010). Epidermal growth factor receptor targeting using cetuximab labeledultrasound contrast agents A feasibility study. In 2010 IEEE International Ultrasonics Symposium, IUS 2010 (pp. 1593-1595). [5935901] https://doi.org/10.1109/ULTSYM.2010.5935901

Epidermal growth factor receptor targeting using cetuximab labeledultrasound contrast agents A feasibility study. / Knowles, Joseph; Heath, Hope; Saini, Reshu; Umphrey, Heidi; Rosenthal, Eben; Hoyt, Kenneth.

2010 IEEE International Ultrasonics Symposium, IUS 2010. 2010. p. 1593-1595 5935901.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Knowles, J, Heath, H, Saini, R, Umphrey, H, Rosenthal, E & Hoyt, K 2010, Epidermal growth factor receptor targeting using cetuximab labeledultrasound contrast agents A feasibility study. in 2010 IEEE International Ultrasonics Symposium, IUS 2010., 5935901, pp. 1593-1595, 2010 IEEE International Ultrasonics Symposium, IUS 2010, San Diego, CA, United States, 10/11/10. https://doi.org/10.1109/ULTSYM.2010.5935901
Knowles J, Heath H, Saini R, Umphrey H, Rosenthal E, Hoyt K. Epidermal growth factor receptor targeting using cetuximab labeledultrasound contrast agents A feasibility study. In 2010 IEEE International Ultrasonics Symposium, IUS 2010. 2010. p. 1593-1595. 5935901 https://doi.org/10.1109/ULTSYM.2010.5935901
Knowles, Joseph ; Heath, Hope ; Saini, Reshu ; Umphrey, Heidi ; Rosenthal, Eben ; Hoyt, Kenneth. / Epidermal growth factor receptor targeting using cetuximab labeledultrasound contrast agents A feasibility study. 2010 IEEE International Ultrasonics Symposium, IUS 2010. 2010. pp. 1593-1595
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abstract = "This paper details the potential of cetuximab (C225) labeled microbubbles(MBs) to improve ultrasound (US) imaging of head and neck squamous cellcarcinoma (HNSCC). C225 is a therapeutic monoclonal antibody to the epidermalgrowth factor receptor (EGFR) and currently approved for the treatment ofrecurrent HNSCC. Conjugating C225 to the surface of US MBs produces a targetedcontrast agent that selectively binds to over-expressed EGFR on the tumorendothelium to improve visualization and therapeutic monitoring. Analysis oftargeted MB binding in vitro was performed using SCC-1 and normal dermalfibroblasts (NDF) cell lines. Cells were incubated with MBs conjugated to eitherC225 or IgG isotype control antibodies. Light microscopy was used to quantifyMB receptor binding. Attached MB were normalized by cell count and recorded foreach group. To evaluate C225-labeled MBs in an animal model, SCC-1 cells wereimplanted in the flank of nude athymic mice (N=8). MBs labeled with C225 orcontrol antibodies were administered via a bolus tail vein injection and tumorswere examined using a MB sensitive harmonic imaging mode. For each tumor, USimages from the targeted and control groups were paired and assessed by ablinded reviewer to determine greatest degree of intratumoral contrastenhancement. MBs labeled with C225 exhibited significantly higher SCC-1 cellattachment levels relative to control group measurements (p=0.001).Specifically, the mean number of attached MBs per cell was 3.6±0.7 and0.7±0.1 for the C225-and control antibody-labeled groups, respectively,yielding nearly a 6-fold difference. Given presentation of paired animal data,it was determined that 75{\%} (6 of 8) of the US images from the C225-labeled MBexperimental day exhibited increased enhancement compared to the same animalsadministered control MBs. This study demonstrates feasibility of targeted USimaging of HNSCC using cetuximab-labeled MBs.",
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