Targeted Contrast Agents
1. Targeted NIR contrast agents
Over the past decade, optical imaging using near-infrared (NIR) fluorescent light has received considerable interest. Targeted fluorophores are the main area of interest, which can be used for image-guided surgery by specifically visualizing target tissue with high optical properties while avoiding nonspecific uptake in normal background tissues. We have been systematically probing the relationship among the hydrodynamic diameter, shape, charge, and hydrophobicity of contrast agents on their in vivo biodistribution and clearance. Using invisible NIR fluorescence imaging and 3D molecular modeling, we have defined the relationship among the key independent variables that dictate biodistribution and tissue-specific targeting to tissues such as the lung and sentinel lymph nodes, human prostate cancers, and human melanomas. We recently developed a new pharmacophore design strategy called “structure-inherent targeting,” where tissue- and/or organ-specific targeting is engineered directly into the non-resonant structure of NIR fluorophores, thus creating the most compact optical contrast agents as possible for biomedical imaging.
2. Targeted NIR-PET contrast agents
The progressive breakthroughs in medical imaging have supported the development of multimodal and molecular imaging approaches for a better understanding of disease diagnosis and treatment. To accelerate the development and clinical translation of promising novel therapeutic agents, we are currently working to translate our tissue-specific nuclear-NIR agents into the clinic by augmenting the polymethine and oxazine chemical scaffolds with PET and SPECT radiolabels for both noninvasive preclinical imaging and intraoperative image-guided surgery.
Relevant Publications
Choi HS, Nasr K, Alyabyev S, Feith D, Lee JH, Kim SH, Ashitate Y, Hyun H, Patonay G, Strekowski L, Henary M, Frangioni JV. Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. Angew Chem Int Ed. 2011; 50(28): 6258-63. PMCID: PMC3128676.
Hyun H, Wada H, Bao K, Gravier J, Owens EA, Laramie M, Henary M, Frangioni JV, Choi HS. Phosphonated near-infrared fluorophores for biomedical imaging of bone. Angew Chem Int Ed. 2014; 53(40): 10668-72. PMCID: PMC4221277.
Bao K, Nasr KA, Hyun H, Lee JH, Gravier J, Gibbs SL, Choi HS. Charge and hydrophobicity effects of NIR fluorophores on bone-specific imaging. Theranostics. 2015; 5(6): 609-17. PMCID: PMC4377729.
Hyun H, Park MH, Owens EA, Wada H, Henary M, Frangioni JV, Choi HS. Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging. Nat Med. 2015; 21: 192-7. PMCID: PMC4319985.
Park GK, Lee JH, Soriano E, Choi M, Bao K, Katagiri W, Kim DY, Paik JH, Yun SH, Frangioni JV, Clancy TE, Kashiwagi S, Henary M, Choi HS. Rapid and selective targeting of heterogeneous pancreatic neuroendocrine tumors. iScience. 2020; 23(4): 101006. PMCID: PMC7139119.
Research Team
Leader: Kai Bao, Ph.D., Assistant Professor of Radiology
Members
Chengeng Yang, M.S., Research Assistant
Haoran Wang, M.S., Visiting Graduate Student
Sung Ahn, B.A., Research Assistant
Kevin Cardenas, B.S. Candidate, Research Student
Surbhi Srinivas, B.S. Candidate, Research Student