title: Direct quantitative13C-filtered1H magnetic resonance imaging of PEGylated biomacromolecules in vivo.
abstract: 1H MRI is an established diagnostic method that generally relies on detection of water. Imaging specific macromolecules is normally accomplished only indirectly through the use of paramagnetic tags, which alter the water signal in their vicinity. We demonstrate a new approach in which macromolecular constituents, such as proteins and drug delivery systems, are observed directly and quantitatively in vivo using1H MRI of13C-labeled poly(ethylene glycol) (13C-PEG) tags.
  
  
  
  Molecular imaging of13C-PEG-labeled species was accomplished by incorporating a modified heteronuclear multiple quantum coherence filter into a gradient echo imaging sequence. We demonstrate the approach by monitoring the real-time distribution of13C-PEG and13C-PEGylated albumin injected into the hind leg of a mouse.
  
  
  
  Filtering the1H PEG signal through the directly coupled13C nuclei largely eliminates background water and fat signals, thus enabling the imaging of molecules using1H MRI.
  
  
  
  PEGylation is widely employed to enhance the performance of a multitude of macromolecular therapeutics and drug delivery systems, and13C-filtered1H MRI of13C-PEG thus offers the possibility of imaging and quantitating their distribution in living systems in real time. Magn Reson Med 77:1553-1561, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
authors.affiliation: Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada.
authors.forename: Rohan D A
authors.initials: RD
authors.lastname: Alvares
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Justin Y C
authors.initials: JY
authors.lastname: Lau
authors.affiliation: Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Macdonald
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Cunningham
authors.affiliation: Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada.|Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Prosser
mesh_terms: D000465:Algorithms; D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D007553:Isotope Labeling; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D053769:Nanocapsules / Q000032:analysis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000032:analysis* / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted
chemical_list: D053769:Nanocapsules; D011092:Polyethylene Glycols
keywords: 13C-filtered 1H MRI; HMQC filter; MRI; PEG; contrast agent; molecular imaging