Unlock instant, AI-driven research and patent intelligence for your innovation.

Protease-activated contrast agents for in vivo imaging

A quencher and compound technology, applied in the field of protease-activated contrast agents for in vivo imaging, can solve the problems of lack of probes and limitations of probes in tumor contrast

Pending Publication Date: 2020-01-10
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
View PDF22 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although all reported protease-triggered smart probes have been demonstrated to be useful for imaging tumor margins in mouse models of cancer (Verdoes et al. (2013) J.Am.Chem.Soc.135:14726-30; Hu et al. ( 2014) Angew.Chem.Int.Ed.Engl.53:7669-73; Mito et al. (2012) Cancer 118:5320-30), but all probes have limitations in tumor contrast and have not been clinically Approved probes for use with imaging instruments

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Protease-activated contrast agents for in vivo imaging
  • Protease-activated contrast agents for in vivo imaging
  • Protease-activated contrast agents for in vivo imaging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0240] Design and Synthesis of Quenched Fluorescent Substrates

[0241] The recently reported chemical structures of a series of potent and selective ABPs (exemplified by compound 1 below) were used as a starting point for designing the quenched fluorogenic substrate probes reported here. See Verdo et al. (2013) J.Am.Chem.Soc. 135:14726-30 and PCT International Publication No. WO2014 / 145257.

[0242]

[0243] As part of the design process, the ability of the substrate to generate a signal without inhibiting the target protease was determined, which, combined with improved water solubility, allows for faster in vivo activation of substrate analogs and higher yields than original covalent probes. bright signal. Using an enzymatically cleavable amide bond to replace the irreversible thiol-reactive tetrafluorophenoxymethylketone (PMK) electrophile ( Figure 1A ). To select optimal substrates for cathepsin activity imaging, a 6-member library of quenched fluorescent substra...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Compounds useful as contrast agents in image-guided surgery are provided. The compounds comprise a latent cationic lysosomotropic fragment that is detectable upon cleavage by lysosomal proteases within treated tissues, particularly within tumors and other diseased tissues. Also provided are compositions comprising the compounds and methods for using the compounds, for example in dynamically monitoring protease activity in vivo during image-guided tumor resection surgery.

Description

[0001] cross reference [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 478,639, filed March 30, 2017, the entire disclosure of which is incorporated herein by reference. [0003] Statement of Government Support [0004] This invention was made with government support under contracts EB005011 and HL116307 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0005] Surgical intervention is currently the most common treatment for almost all types of solid tumors. Siegel et al. (2012) CA Cancer J. Clin. 62:220-41; DeSantis et al. (2014) CA Cancer J. Clin. 64:252-71. Thus, a successful outcome depends on the complete removal of all cancer cells during surgery, both from the affected major organs and from potential metastatic sites. Vahrmeier et al. (2013) Nat. Rev. Clin. Oncol. 10:507-18. Contrast agents targeting specific biomarkers in cancer could be used as intraoperativ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/14C12Q1/37
CPCC07D403/06C07D403/14G01N33/532G01N33/58C09B23/0066C09B23/086C07K5/06078A61K49/0056C07D403/12A61K49/006A61K49/0052A61K2123/00G01N33/582
Inventor 马修·S·博焦马蒂金·韦尔多斯莱斯莉·奥弗里尼马里·P·维索娜
Owner THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV