Thursday 10 Nov 2016Nanoscale MRI Contrast Agents: Design Features for Exceptional Performance

Dr Gemma-Louise Davies - University of Warwick

HAR/170 (3D Visualisation Suite)  12:30-13:30

Magnetic resonance imaging (MRI) is a powerful non-invasive technique which becomes considerably more potent when contrast agents (CAs) are introduced.[1] Current clinically-approved molecular CAs, however, often suffer from poor signal-to-noise, necessitating high dosages and leading to patient safety concerns. CAs based on nanomaterials have unparalleled capabilities to enhance this vital tool, using markedly lower doses than traditional species, thanks to their unique sizes, colloidal behaviour and effective interaction with water.[2] In this talk, the careful design and engineering of nanoscale contrast agents (both positive and negative) which demonstrate exceptionally strong contrast enhancement will be described.
Positive nanoparticulate CAs have been prepared through covalent incorporation of gadolinium chelates into mesoporous silica nanoparticles (MSNs), resulting in strong relaxation enhancement compared to ‘molecular scale’ equivalents, due to the reduced tumbling rates associated with particles. Enhancement can be further improved through careful control of chelate localisation within the porous MSN network. Loading Gd-DOTA chelates on internal MSN walls have generated T1 MRI relaxation characteristics (r1=39.26±1.29 mM-1s-1 at 3 T) which are 20-fold stronger than clinically-used molecular Gd-DOTA, at exceptionally low Gd(III) loadings (just 1.37 wt%).[3]
Superparamagnetic iron oxide nanoparticles have seen application as negative MRI CAs, and have previously been applied in the clinic, though their popularity has plummeted in recent years. Herein, an in situ procedure has been used to prepare colloids of ferrite nanoparticles, exploiting charged polyelectrolyte species as templating stabilisers. These stable colloids demonstrate exceptionally strong MRI contrast capabilities, particularly at low fields (r1 values of 34.80 mM-1s-1 at 20 MHz and 88.43 mM-1s-1 at 0.01 MHz), which outperform the current clinical standards.[4] Relaxometric investigations using nuclear magnetic resonance dispersion (NMRD) techniques demonstrate that this behaviour is due to interparticle interactions, thanks to the templating effect of the polymer. The stable colloidal nanoparticles have also been shown to prevent protein-adsorption triggered thrombosis, which causes unexpected (and potentially fatal) problems in the clinic.
These positive and negative contrast agent species, which demonstrate relaxation behaviour superior to their molecular and clinically-approved analogues, show strong potential for in vivo MRI diagnostics.

[1] P. Caravan, Chem. Soc. Rev., 35(6) (2006) 512.
[2] G.-L. Davies, I. Kramberger, J.J. Davis, Chem. Commun., 49(84) (2013) 9704.
[3] J.J. Davis, W.-Y. Huang, G.-L. Davies, J. Mater. Chem., 22 (2012) 22848.
[4] L. Ternent, D.A. Mayoh, M.R. Lees, G.-L. Davies, J. Mater. Chem. B, 4 (2016) 3065.

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