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


METHODS
Preclinical blinded assessment of anti-EGFR and anti-CD147 microbubble contrast agents for US imaging of HNSCC.


METHODS
Animal study.


METHODS
Immunodeficient mice.


METHODS
Injection of targeted microbubbles.


METHODS
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) (R(2) = 0.81) and CD147 (R(2) = 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.


CONCLUSIONS
This preclinical study demonstrates feasibility of using molecular US to target HNSCC for contrast-enhanced imaging of HNSCC tumor in vivo.
Department of Surgery, University of Alabama at Birmingham, 35294-0012, USA.
Joseph A
JA
Knowles
Cara H
CH
Heath
Reshu
R
Saini
Heidi
H
Umphrey
Jason
J
Warram
Kenneth
K
Hoyt
Eben L
EL
Rosenthal
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology; D051926:Basigin / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003287:Contrast Media / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D007124:Immunoenzyme Techniques; D016014:Linear Models; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D012680:Sensitivity and Specificity; D019809:Streptavidin / Q000494:pharmacology; D014463:Ultrasonography
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C497887:Bsg protein, mouse; D003287:Contrast Media; D051926:Basigin; D019809:Streptavidin; D066246:ErbB Receptors; D016650:Fluorescein-5-isothiocyanate; D000068818:Cetuximab