Structure-Inherent Targeting of NIR Fluorophores for Parathyroid and Thyroid Gland Imaging

Abstract

The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible create tissue-specific near-infrared fluorophores using the inherent chemical structure. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head/neck surgery, the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake in the specific glands after a single intravenous injection of only 0.06 mg kg−1 in a pig. Using a dual-channel near-infrared imaging system, we demonstrate the real-time, high-sensitivity, unambiguous identification of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays the foundation for head/neck surgery performed with increased precision and efficiency, and potentially lowers morbidity, and a general strategy for targeted near-infrared fluorophore development.