Rapid and Selective Targeting of Heterogeneous Pancreatic Neuroendocrine Tumors

• Published in: iScience Vol. 23; no. 4; p. 101006
• Main Authors: Park, G. Kate, Lee, Jeong Heon, Soriano, Eduardo, Choi, Myunghwan, Bao, Kai, Katagiri, Wataru, Kim, Do-Yeon, Paik, Ji-Hye, Yun, Seok-Hyun, Frangioni, John V., Clancy, Thomas E., Kashiwagi, Satoshi, Henary, Maged, Choi, Hak Soo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.04.2020; Elsevier
• Subjects: Cancer; Chemistry; Histology; Chemistry; Histology; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101006

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. [Display omitted] •Bioengineered near-infrared fluorescent small molecules for PNET imaging•Highlight tumors within a minute after a single bolus injection with improved retention•Sensitive and specific detection of ultrasmall ectopic tumors•Intraoperative image-guided navigation provides a surgical margin Histology; Chemistry; Cancer