Rapid and Selective Targeting of Heterogeneous Pancreatic Neuroendocrine Tumors

G Kate Park; Jeong Heon Lee; Eduardo Soriano; Myunghwan Choi; Kai Bao; Wataru Katagiri; Do-Yeon Kim; Ji-Hye Paik; Seok-Hyun Yun; John V Frangioni; Thomas E Clancy; Satoshi Kashiwagi; Maged Henary; Hak Soo Choi

doi:10.1016/j.isci.2020.101006

Rapid and Selective Targeting of Heterogeneous Pancreatic Neuroendocrine Tumors

iScience. 2020 Apr 24;23(4):101006. doi: 10.1016/j.isci.2020.101006. Epub 2020 Mar 25.

Authors

Affiliations

¹ Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
² Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave SE, Atlanta, Georgia 30303, USA.
³ Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, MA 02139, USA.
⁴ Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
⁵ Curadel, LLC, Natick, MA 01760, USA.
⁶ Division of Surgical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA 02215, USA.
⁷ Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave SE, Atlanta, Georgia 30303, USA. Electronic address: mhenary1@gsu.edu.
⁸ Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: hchoi12@mgh.harvard.edu.

Abstract

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.

Keywords: Cancer; Chemistry; Histology.