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Home Conference IITS 2019  targeted Contrast Agents for Image-Guided Thoracic Surgery
targeted Contrast Agents for Image-Guided Thoracic Surgery
Prof. HakSoo Choi Massachusetts General Hospital, Harvard Medical School | Republic of Korea Speciality : Department of Radiology

Two fundamental and unsolved problems facing image-guided surgery are nonspecific uptake of intravenously administered diagnostic agents by normal tissues and organs, and incomplete elimination of unbound targeted agents from the body. To solve these problems, we have synthesized a series of indocyanine near-infrared (NIR) fluorophores that varied systematically in net charge, conformational shape, hydrophilicity/lipophilicity, and charge distribution. Using 3D molecular modeling and optical fluorescence imaging, we have defined the relationship among the key independent variables that dictate biodistribution and tissue-specific targeting such as lung and sentinel lymph nodes (Nat Biotechnol. 2010), human prostate cancers (Nat Nanotechnol. 2010), and human melanomas (Nat Biotechnol. 2013). Recently,

we have developed new pharmacophore design strategy “structure-inherent targeting,” where tissue- and/or organspecific targeting is engineered directly into the non-resonant structure of a NIR fluorophore, thus creating the most compact possible optical contrast agent for bioimaging and nanomedicine (Angew Chem. 2015, Nat Med. 2015). The biodistribution and targeting of these compounds vary with dependence on their unique physicochemical descriptors and cellular receptors, which permit 1) selective binding to the target tissue/organ, 2) visualization of the target specifically and selectively, and 3) provide curing options such as image-guided surgery or photo dynamic therapy. Our study solves two fundamental problems associated with fluorescence image-guided surgery and lays the foundation for additional targeted agents with optimal optical and in vivo performance.

Nanotechnology; Optical Imaging; Diagnostic Imaging; Tumor Targeting; Near-Infrared Fluorophore; Biodistribution; Clearance; Image-guided Surgery
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