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Quantification of water exchange kinetics for targeted PARACEST perfluorocarbon nanoparticles
Author(s) -
Cai Kejia,
Kiefer Garry E.,
Caruthers Shelton D.,
Wickline Samuel A.,
Lanza Gregory M.,
Winter Patrick M.
Publication year - 2012
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1746
Subject(s) - nanoparticle , chemistry , kinetics , small molecule , molecular imaging , magnetic particle imaging , nuclear magnetic resonance , magnetic nanoparticles , nanotechnology , in vivo , materials science , biochemistry , physics , microbiology and biotechnology , quantum mechanics , biology
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 19 F signal for measuring particle binding with high signal intensity and no background signal. 19 F 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, 19 F and PARACEST, for quantitative targeted molecular imaging of fibrin. Copyright © 2011 John Wiley & Sons, Ltd.