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Evaluating size‐dependent relaxivity of PEGylated‐USPIOs to develop gadolinium‐free T1 contrast agents for vascular imaging
Author(s) -
Khandhar Amit P.,
Wilson Gregory J.,
Kaul Michael G.,
Salamon Johannes,
Jung Caroline,
Krishnan Kannan M.
Publication year - 2018
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.36438
Subject(s) - materials science , gadolinium , peg ratio , polyethylene glycol , in vivo , mri contrast agent , magnetic resonance imaging , biomedical engineering , dispersity , nuclear magnetic resonance , radiology , medicine , chemistry , physics , microbiology and biotechnology , organic chemistry , finance , economics , metallurgy , biology , polymer chemistry
Ultra‐small superparamagnetic iron oxide (USPIO) nanoparticles provide a safer alternative to gadolinium‐based contrast agents (GBCAs) in T1‐weighted MR imaging. MRI contrast behavior of USPIOs depends on their magnetic properties, which in turn depend on their physicochemical composition. Identifying and tailoring USPIO structural characteristics that influence proton relaxation in MRI is crucial to developing effective gadolinium‐free T1 contrast agents. Here, we present a systematic empirical evaluation of the relationship between USPIO size and MRI relaxivity ( r 1 and r 2 values). Monodisperse USPIO cores, with precisely controlled core diameter ( d C ) were synthesized via the thermal decomposition of iron(III)‐oleate precursor. USPIOs with d C = 6.34, 7.58, 8.58, and 9.50nm, were dispersed in aqueous phase via ligand exchange with silane or dopamine‐modified polyethylene glycol (PEG) polymers. Relaxivity characterization in a 1.5 T clinical MRI scanner showed the r 2 / r 1 ratio increased linearly with USPIO core diameter ( R 2 = 0.95), but varied little with both hydrodynamic diameter ( d H ) and PEG molecular weight. One sample, DOPA‐6‐20 (6.34nm USPIO cores coated with 20 kDa dopamine‐modified PEG), provided the lowest r 2 / r 1 value (3.44) and thus promise as a potential T1 contrast agent. In a preliminary study, we evaluated DOPA‐6‐20 for in vivo angiography imaging in a mouse with a 7 T scanner and observed strong T1‐weighted enhancement of the mouse blood pool. Key anatomical features in the vascular network were visible even 5 min after intravenous administration. Using empirical data, we have presented the basis of a structure–property relationship that can help develop optimized USPIO‐based T1 contrast agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2440–2447, 2018.