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
Affiliations
G. Kate Park
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Jeong Heon Lee
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Eduardo Soriano
Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave SE, Atlanta, Georgia 30303, USA
Myunghwan Choi
Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, MA 02139, USA
Kai Bao
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Wataru Katagiri
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Do-Yeon Kim
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA
Ji-Hye Paik
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA
Seok-Hyun Yun
Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, MA 02139, USA
John V. Frangioni
Curadel, LLC, Natick, MA 01760, USA
Thomas E. Clancy
Division of Surgical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA 02215, USA
Satoshi Kashiwagi
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Maged Henary
Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave SE, Atlanta, Georgia 30303, USA; Corresponding author
Hak Soo Choi
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Corresponding author
Summary: 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. : Histology; Chemistry; Cancer Subject Areas: Histology, Chemistry, Cancer
