Molecular imaging of oral premalignant and malignant lesions using fluorescently labeled lectins

John Baeten; Amritha Suresh; Alexander Johnson; Ketan Patel; Moni Kuriakose; Anita Flynn; Deepak Kademani

doi:10.1016/j.tranon.2014.02.006

Molecular imaging of oral premalignant and malignant lesions using fluorescently labeled lectins

Transl Oncol. 2014 Apr;7(2):213-20. doi: 10.1016/j.tranon.2014.02.006. Epub 2014 Mar 4.

Authors

John Baeten¹, Amritha Suresh², Alexander Johnson¹, Ketan Patel³, Moni Kuriakose², Anita Flynn², Deepak Kademani⁴

Affiliations

¹ Inter-Med Inc., Vista Dental Products, 2200 Northwestern Ave., Racine, WI 53404, USA.
² Mazumdar-Shaw Cancer Center, Department of Head and Neck Oncology, Narayana Health City, 258/A, Bommasandra Industrial Area, Anekal Taluk 560 099, Bangalore, India.
³ University of Minnesota, Department of Oral and Maxillofacial Surgery, Moos Tower 7-174G, 515 Delaware Street, Minneapolis, MN 55455, USA.
⁴ University of Minnesota, Department of Oral and Maxillofacial Surgery, Moos Tower 7-174G, 515 Delaware Street, Minneapolis, MN 55455, USA. Electronic address: kadem001@umn.edu.

Abstract

Aberrant glycosylation during carcinogenesis results in altered glycan expression on oral cancer cells. The objective of this study was to detect this atypical glycosylation via imaging of fluorophore-conjugated lectins. Paired normal and tumor tissue from seven patients with oral squamous cell carcinoma were investigated for sialic acid expression via the legume protein wheat germ agglutinin (WGA). Fluorophore (Alexa Fluor 350 and Alexa Fluor 647) conjugated WGA was topically applied to the tissue samples and imaged using a custom wide-field fluorescence imaging system. All seven patients had histologically confirmed disease with 6/7 exhibiting squamous cell carcinoma and 1/7 exhibiting dysplasia. Fluorescent data collected from all patients demonstrated that fluorophore conjugated WGA could distinguish between pathologically normal and diseased tissue with the average signal-to-noise ratio (SNR) among all patients being 5.88 (P = .00046). This SNR was statistically significantly higher than the SNR from differences in tissue autofluorescence (P = .0049). A lectin inhibitory experiment confirmed that lectin binding is molecularly specific to overexpressed tumor glycans and that fluorescence is not due to tissue optical properties or tissue diffusion differences. These results illustrate that changes in tumor glycan content of oral neoplasms can be detected with optical imaging using topically applied fluorescently labeled WGA. Lectin targeting of oral lesions using optical imaging may provide a new avenue for the early detection of oral cancers.