In Vivo-Near Infrared Imaging of Neurodegeneration

Methods Mol Biol. 2017:1658:253-262. doi: 10.1007/978-1-4939-7244-9_17.

Abstract

In vivo near-infrared (NIR) imaging of molecular processes at the preclinical stage promises to provide more valuable mechanistic information about pathological pathways involved in neurodegeneration. NIR imaging has the potential to improve in vivo therapeutic screening protocols by enabling noninvasive monitoring of presymptomatic responses to treatment. We have developed new NIR fluorescent contrast agents conjugated to markers of cell death, and using these agents we have identified molecular pathways associated with prion-induced neurodegeneration and determined the optimal window for meaningful therapeutic intervention in prion disease. This chapter provides a description of the synthesis and purification of our NIR cell Death (NIRD) contrast agent and the application of in vivo NIRD (iNIRD) imaging to a prion model of neurodegeneration.

Keywords: Caspase; Fluorescence; Imaging; In vivo; Near infrared; Neurodegeneration; Prion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / chemistry
  • Amino Acid Chloromethyl Ketones / pharmacokinetics
  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Brain / pathology
  • Caspase Inhibitors / chemistry
  • Caspase Inhibitors / pharmacokinetics
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Death
  • Contrast Media / chemical synthesis*
  • Contrast Media / pharmacokinetics
  • Injections, Intravenous
  • Mice
  • Molecular Imaging / methods*
  • Prion Diseases / diagnostic imaging*
  • Prion Diseases / genetics
  • Prion Diseases / metabolism
  • Prion Diseases / pathology
  • Spectroscopy, Near-Infrared / methods*
  • Staining and Labeling / methods*
  • Succinimides / chemistry

Substances

  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Contrast Media
  • Succinimides
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Caspases