Imaging inflammation using an activated macrophage probe with Slc18b1 as the activation-selective gating target

Nat Commun. 2019 Mar 7;10(1):1111. doi: 10.1038/s41467-019-08990-9.

Abstract

Activated macrophages have the potential to be ideal targets for imaging inflammation. However, probe selectivity over non-activated macrophages and probe delivery to target tissue have been challenging. Here, we report a small molecule probe specific for activated macrophages, called CDg16, and demonstrate its application to visualizing inflammatory atherosclerotic plaques in vivo. Through a systematic transporter screen using a CRISPR activation library, we identify the orphan transporter Slc18b1/SLC18B1 as the gating target of CDg16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines
  • Animals
  • CRISPR-Cas Systems
  • Cation Transport Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Inflammation / diagnostic imaging*
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Macrophage Activation*
  • Mice
  • Mice, Knockout, ApoE
  • Molecular Probe Techniques
  • Molecular Probes
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plaque, Atherosclerotic / immunology
  • Plaque, Atherosclerotic / metabolism
  • RAW 264.7 Cells

Substances

  • Acridines
  • Cation Transport Proteins
  • Molecular Probes
  • vesicular polyamine transporter, mouse