Rapid and selective targeting of heterogeneous pancreatic neuroendocrine tumors


G. K. Park, J. H. Lee, E. Soriano, M. Choi, K. Bao, W. Katagiri, D. Y. Kim, J. H. Paik, S. H. Yun, J. V. Frangioni, T. E. Clancy, S. Kashiwagi, M. Henary, and H. S. Choi. 2020. “Rapid and selective targeting of heterogeneous pancreatic neuroendocrine tumors.” iScience, 23, Pp. 101006.


Design of tissue-specific contrast agents to delineate tumors from background tissues is a major unmet clinical need for ultimate surgical interventions. Bioconjugation of fluorophore(s) to a ligand has been mainly used to target overexpressed receptors on tumors. However, the size of the final targeted ligand can be large, >20 kDa, and cannot readily cross the microvasculature to meet the specific tissue, resulting in low targetability with a high background. Here, we report a small and hydrophilic phenoxazine with high targetability and retention to pancreatic neuroendocrine tumor. This bioengineered fluorophore permits sensitive detection of ultrasmall (<0.5 mm) ectopic tumors within a few seconds after a single bolus injection, highlighting every tumor in the pancreas from the surrounding healthy tissues with reasonable half-life. The knowledge-based approach and validation used to develop structure-inherent tumor-targeted fluorophores have a tremendous potential to improve treatment outcome by providing definite tumor margins for image-guided surgery.


Park, G KateLee, Jeong HeonSoriano, EduardoChoi, MyunghwanBao, KaiKatagiri, WataruKim, Do-YeonPaik, Ji-HyeYun, Seok-HyunFrangioni, John VClancy, Thomas EKashiwagi, SatoshiHenary, MagedChoi, Hak SooengiScience. 2020 Mar 25;23(4):101006. doi: 10.1016/j.isci.2020.101006.