Design, synthesis and application of near-infrared fluorescence probe IR-780-Crizotinib in detection of ALK positive tumors

Protein Expr Purif. 2021 Nov:187:105952. doi: 10.1016/j.pep.2021.105952. Epub 2021 Aug 7.

Abstract

At present, the early diagnosis and treatment of NSCLC has become an international research hotspot. However, how to realize the organic combination of highly sensitive and high-resolution tumor imaging diagnosis and effective treatment, and to provide effective information for the diagnosis and treatment of cancer is still a major problem in the integration of cancer diagnosis and treatment. In this study, based on the Crizotinib has a good targeted inhibitory effect on ALK positive tumor cells, the near-infrared targeted fluorescent dye IR-780 was covalently bound with the drug molecule Crizotinib, thus the near-infrared fluorescent probe IR-780-Crizotinib targeting ALK positive tumor cells was synthesized. The probe structure is confirmed by NMR and MS. The optical properties of the fluorescent probe and the imaging process in ALK positive tumor-bearing mice were analyzed using ultraviolet spectrophotometer, near-infrared fluorescence spectrometer, and near-infrared fluorescence imaging system. The results show that the probe had better photoactivity. In vivo imaging shows that the probe maintained the biological activity of Crizotinib, effectively targeting the tumor site involved with clear imaging, and ultimately excreted from the body. It was confirmed that the probe could be used for the tracking, positioning and targeted therapy of nude mice with ALK positive tumors in vivo, thus exploring a new approach for the clinical application of near-infrared fluorescent probe to detect ALK positive tumors in the future.

Keywords: ALK Positive tumors; Crizotinib; Fluorescence imaging; IR-780; Near-infrared fluorescent probe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Cell Line, Tumor
  • Crizotinib / chemistry*
  • Crizotinib / pharmacology
  • Fluorescent Dyes / chemistry*
  • Humans
  • Indoles / chemical synthesis*
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy
  • Male
  • Mice
  • Mice, Nude
  • Optical Imaging
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / metabolism
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Spectroscopy, Near-Infrared

Substances

  • 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium
  • Antineoplastic Agents
  • Fluorescent Dyes
  • Indoles
  • Protein Kinase Inhibitors
  • Crizotinib
  • Receptor Protein-Tyrosine Kinases