Theranostics 2019; 9(4):1085-1095. doi:10.7150/thno.29719

Research Paper

Zwitterionic near-infrared fluorophore-conjugated epidermal growth factor for fast, real-time, and target-cell-specific cancer imaging

Hyunjin Kim1, Mi Hyeon Cho1, Hak Soo Choi2, Byung Il Lee1, Yongdoo Choi1,✉

1. Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea
2. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Abstract

Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, which is associated with metastatic potential and poor prognosis in cancer patients. Therefore, development of EGFR-targeted sensitive imaging probes has been a challenge in tumor targeting, image-guided cancer surgery, patient-selective anti-EGFR therapy, and efficient targeted therapies.

Methods: We synthesized a zwitterionic near-infrared fluorophore (ATTO655)-conjugated epidermal growth factor (EGF) as a novel activatable molecular probe. Fluorescence OFF/ON property and EGFR-targeting specificity of EGF-ATTO655 as well as its utility in real-time near-infrared (NIR) fluorescence imaging of EGFR-positive cancers were evaluated using in vitro and in vivo studies.

Results: When conjugated to EGF, the fluorescence of ATTO655 quenched efficiently by photo-induced electron transfer (PET) mechanism between the conjugated dyes and nearby amino acid quenchers (tryptophan/tyrosine residues), which was stably maintained at physiological pH and in the presence of serum for at least 17 h. The fluorescence of EGF-ATTO655 turned on by receptor-mediated endocytosis and subsequent disintegration of EGF in EGFR-positive A431 cancer cells, thereby enabling specific and real-time fluorescence imaging of EGFR-positive cancer cells. Consequently, EGFR-positive tumors could be clearly visualized 3 h post-injection with a significantly high tumor-to-background ratio (TBR = 6.37).

Conclusion: This PET mechanism-based OFF/ON type of EGF probe showed great potential for rapid, real-time, and target-cell-specific imaging of EGFR-overexpressing cancers in vitro and in vivo.

Keywords: Epidermal growth factor, photo-induced electron transfer, tumor-specific targeting, real-time cancer imaging

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Kim H, Cho MH, Choi HS, Lee BI, Choi Y. Zwitterionic near-infrared fluorophore-conjugated epidermal growth factor for fast, real-time, and target-cell-specific cancer imaging. Theranostics 2019; 9(4):1085-1095. doi:10.7150/thno.29719. Available from http://www.thno.org/v09p1085.htm