Quantification of water exchange kinetics for targeted PARACEST perfluorocarbon nanoparticles

Kejia Cai, Garry E. Kiefer, Shelton D. Caruthers, Samuel A. Wickline, Gregory M. Lanza, Patrick M. Winter

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

PARACEST (PARAmagnetic Chemical Exchange Saturation Transfer) agents offer the ability to generate "contrast on demand", negating the need to image before contrast agent injection. Perfluorocarbon (PFC) nanoparticles can deliver very large payloads of PARACEST agents, lowering the effective detection limit for molecular imaging of sparse biomarkers. Also, the PFC core provides a quantitative 19F signal for measuring particle binding with high signal intensity and no background signal. 19F quantization coupled with mathematical modeling of the PARACEST signal showed that incorporating PARACEST chelates onto the nanoparticle surface reduces the bound water lifetime and diminishes the available contrast to noise ratio compared to the parent small molecule PARACEST chelate. PARACEST nanoparticles were targeted to fibrin, an early biomarker for atherosclerotic plaque rupture, and bound to the surface of in vitro clots, yielding a detection limit of 2.30 nM at 11.7T. When the particles bind to a target surface, the image contrast is higher than predicted from phantom experiments, perhaps due to improved water exchange kinetics. We demonstrated that PARACEST PFC nanoparticles can provide two unique signatures, 19F and PARACEST, for quantitative targeted molecular imaging of fibrin.

Original languageEnglish
Pages (from-to)279-285
Number of pages7
JournalNMR in biomedicine
Volume25
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Fibrin
  • Fluorine
  • Nanoparticle
  • PARACEST

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