Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent

Keith W. MacRenaris, Zhidong Ma, Ruby L. Krueger, Christiane E. Carney, Thomas J. Meade*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Calcium [Ca(II)] is a fundamental transducer of electrical activity in the central nervous system (CNS). Influx of Ca(II) into the cytosol is responsible for action potential initiation and propagation, and initiates interneuronal communication via release of neurotransmitters and activation of gene expression. Despite the importance of Ca(II) in physiology, it remains a challenge to visualize Ca(II) flux in the central nervous system (CNS) in vivo. To address these challenges, we have developed a new generation, Ca(II)-activated MRI contrast agent that utilizes ethyl esters to increase cell labeling and prevent extracellular divalent Ca(II) binding. Following labeling, the ethyl esters can be cleaved, thus allowing the agent to bind Ca(II), increasing relaxivity and resulting in enhanced positive MR image contrast. The ability of this probe to discriminate between extra- And intracellular Ca(II) may allow for spatiotemporal in vivo imaging of Ca(II) flux during seizures or ischemia where large Ca(II) fluxes (1-10 μM) can result in cell death.

Original languageEnglish (US)
Pages (from-to)465-473
Number of pages9
JournalBioconjugate Chemistry
Volume27
Issue number2
DOIs
StatePublished - Feb 17 2016

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent'. Together they form a unique fingerprint.

Cite this