Molecular targeting of ultrasonographic contrast agent for detection of head and neck squamous cell carcinoma

Joseph A. Knowles, Cara H. Heath, Reshu Saini, Heidi Umphrey, Jason Warram, Kenneth Hoyt, Eben L. Rosenthal

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objective: To investigate the feasibility of ultrasonographic (US) imaging of head and neck cancer with targeted contrast agents both in vitro and in vivo. We hypothesize that conjugation of microbubble contrast agent to tumor-specific antibodies may improve US detection of head and neck squamous cell carcinoma (HNSCC). Design: Preclinical blinded assessment of anti-EGFR and anti-CD147 microbubble contrast agents for US imaging of HNSCC. Setting: Animal study. Subjects: Immunodeficient mice. Intervention: Injection of targeted microbubbles. Main Outcome Measure: Microbubble uptake in tumors as detected by US. Results: In vitro assessment of anti-epidermal growth factor receptor (EGFR) and anti-CD147-targeted microbubbles in 6 head and neck cancer cell lines yielded a 6-fold improvement over normal dermal fibroblasts (P<.001). Binding of targeted agents had a positive correlation to both epidermal growth factor receptor (EGFR) (R2=0.81) and CD147 (R2=0.72) expression among all cell lines. In vivo imaging of flank tumors in nude mice (N=8) yielded enhanced resolution of anti-EGFR- and anti-CD147-targeted microbubble agents over IgG control (P<.001), while dual-targeted contrast agents offered enhanced imaging over single-targeted contrast agents (P=.02 and P=.05, respectively). In a blinded in vivo assessment, targeted contrast agents increased intratumoral enhancement of flank tumors over controls. Targeted US contrast agents to both EGFR and CD147 were 100% sensitive and 87% specific in the detection of flank tumors. Conclusion: This preclinical study demonstrates feasibility of using molecular US to target HNSCC for contrastenhanced imaging of HNSCC tumor in vivo.

Original languageEnglish (US)
Pages (from-to)662-668
Number of pages7
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume138
Issue number7
DOIs
StatePublished - Jul 1 2012

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Microbubbles
Contrast Media
Epidermal Growth Factor Receptor
Neoplasms
Head and Neck Neoplasms
Neoplasm Antibodies
Cell Line
Feasibility Studies
Carcinoma, squamous cell of head and neck
Nude Mice
Fibroblasts
Immunoglobulin G
Outcome Assessment (Health Care)
Skin
Injections

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology
  • Medicine(all)

Cite this

Molecular targeting of ultrasonographic contrast agent for detection of head and neck squamous cell carcinoma. / Knowles, Joseph A.; Heath, Cara H.; Saini, Reshu; Umphrey, Heidi; Warram, Jason; Hoyt, Kenneth; Rosenthal, Eben L.

In: Archives of Otolaryngology - Head and Neck Surgery, Vol. 138, No. 7, 01.07.2012, p. 662-668.

Research output: Contribution to journalArticle

Knowles, Joseph A. ; Heath, Cara H. ; Saini, Reshu ; Umphrey, Heidi ; Warram, Jason ; Hoyt, Kenneth ; Rosenthal, Eben L. / Molecular targeting of ultrasonographic contrast agent for detection of head and neck squamous cell carcinoma. In: Archives of Otolaryngology - Head and Neck Surgery. 2012 ; Vol. 138, No. 7. pp. 662-668.
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