Endocrine tumors, such as insulinoma, are rare but notoriously difficult to treat surgically due to their small size and poor contrast using white light. Endocrine tumors, such as ovarian cancer, are common but equally difficult to treat surgically, with improved survival dependent on complete cytoreduction. Similarly, normal endocrine tissues, such as the thyroid gland and adrenal gland, can often be difficult to locate during surgery due to adhesions and overlying fascia. Our hypothesis is that near-infrared (NIR) fluorophores targeted to endocrine glands and their tumors will provide surgeons with sensitive, specific, and real-time image- guidance after a single, pre-operative, intravenous injection. When used with an appropriate intraoperative imaging system, NIR fluorescent light from 700 to 900 nm can provide surgeons with real-time localization of normal and diseased tissue, without changing the look of the surgical field. As part of a previously funded Bioengineering Research Partnership (BRP) grant, we have developed the FLARE"""""""" (Fluorescence-Assisted Resection and Exploration) image-guided surgery system. FLARE provides real-time imaging of surgical anatomy (i.e., color video) simultaneously with two independent channels of NIR fluorescent light (700 nm and 800 nm emission). One NIR channel is typically reserved for the tissue to be resected (e.g., tumor) while the other is reserved for tissue that needs to be avoided (e.g., nerves, blood vessels, normal glands, etc.). FLARE has already been translated to the clinic where it is being used in breast cancer sentinel lymph node (SLN) mapping, lung cancer SLN mapping, and plastic surgery. The resection of endocrine gland tumors (e.g., insulinoma and ovarian cancer) and the avoidance of normal endocrine tissue (e.g., thyroid and adrenal glands) represent a significant unmet clinical need, with no available contrast agents. In collaboration with the Henary/Strekowski/Patonay laboratory at Georgia State University, recognized leaders in the field of fluorophore chemistry, we have developed novel NIR fluorophores tailored to endocrine imaging (endocrine-specific NIR fluorophores;ESNFs). Sharing structural and chemical similarities with naturally occurring hormones and drugs, ESNFs provide high contrast for image-guided surgery after a single intravenous injection into mice, rats, and pigs.
The specific aims of this grant are focused on the synthesis of three new chemical classes of ESNFs, scale-up from analytical to preparative production, and optimization of their optical and chemical properties. Completion of these aims will lay the foundation for future clinical testing of ESNFs during image-guided surgery.

Public Health Relevance

Invisible near-infrared fluorescent light can provide sensitive and specific guidance during surgery, but only if optimal contrast agents are available. Endocrine tissues and their tumors are particularly difficult to find during surgery, yet no endocrine-specific near-infrared fluorescent contrast agents presently exist. We have discovered endocrine-specific uptake by certain cyanine and basic aniline near- infrared fluorophores, and in this grant application, describe optimization of these agents and the development of three new families of near-infrared fluorophores for image-guided surgery.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Clinical Molecular Imaging and Probe Development (CMIP)
Program Officer
Krosnick, Steven
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Beth Israel Deaconess Medical Center
United States
Zip Code
Park, G Kate; Hoseok 1st; Kim, Gaon Sandy et al. (2018) Optical spectroscopic imaging for cell therapy and tissue engineering. Appl Spectrosc Rev 53:360-375
Bao, Kai; Lee, Jeong Heon; Kang, Homan et al. (2017) PSMA-targeted contrast agents for intraoperative imaging of prostate cancer. Chem Commun (Camb) 53:1611-1614
Wada, Hideyuki; Hyun, Hoon; Kang, Homan et al. (2017) Intraoperative Near-Infrared Fluorescence Imaging of Thymus in Preclinical Models. Ann Thorac Surg 103:1132-1141
Kang, Homan; Gravier, Julien; Bao, Kai et al. (2016) Renal Clearable Organic Nanocarriers for Bioimaging and Drug Delivery. Adv Mater 28:8162-8168
Ashitate, Yoshitomo; Levitz, Andrew; Park, Min Ho et al. (2016) Endocrine-specific NIR fluorophores for adrenal gland targeting. Chem Commun (Camb) 52:10305-8
Hyun, Hoon; Henary, Maged; Gao, Tielong et al. (2016) 700-nm Zwitterionic Near-Infrared Fluorophores for Dual-Channel Image-Guided Surgery. Mol Imaging Biol 18:52-61
Jee, Joo-Eun; Lim, Jaehong; Ong, Yong Siang et al. (2016) An efficient strategy to enhance binding affinity and specificity of a known isozyme inhibitor. Org Biomol Chem 14:6833-9
Owens, Eric A; Hyun, Hoon; Dost, Tyler L et al. (2016) Near-Infrared Illumination of Native Tissues for Image-Guided Surgery. J Med Chem 59:5311-23
Koo, Heebeom; Lee, Jeong Heon; Bao, Kai et al. (2016) Site-Specific In Vivo Bioorthogonal Ligation via Chemical Modulation. Adv Healthc Mater 5:2510-2516
Owens, Eric A; Henary, Maged; El Fakhri, Georges et al. (2016) Tissue-Specific Near-Infrared Fluorescence Imaging. Acc Chem Res 49:1731-40

Showing the most recent 10 out of 44 publications