Imaging the Distribution of High Colloidal Stability Mesoporous Silica Nanoparticles (MSNs) with PET and MRI

M. Laprise-Pelletier, J.-L. Bridot, R. Guillet-Nicolas, J. Lagueux, Y. Gossuin, S. Laurent, L. Vander Elst, F. Kleitz, M.-A. Fortin
Université Laval, CA

Keywords: mesoporous silica nanoparticles, MRI, PET, gadolinium, 64Cu, biodistribution


Biocompatible and high porosity mesoporous silica nanoparticles (MSNs) represent a significant advance in drug delivery applications, currently entering clinical validation. It will be necessary to track these drug vectors over time with medical imaging techniques. MRI could be used to monitor the blood signal enhancement, and therefore to validate blood retention of i.v.-injected MSNs. On the other hand, high-sensitivity PET would allow the quantitative and dynamic monitoring of nanoparticle biodistribution, a promising application of new PET/MRI systems. Here are for the first time presented dynamic MSN biodistribution data with MRI and PET. A recently developed high colloidal stability MSN system showing an intricate 3-D porous network, narrow particle size distribution (140 nm mean diam.) and very high porosity (up to 70% vol.), was grafted with DTPA enabling efficient chelation of 64Cu2+ and Gd3+. An efficient size-exclusion chromatography procedure was developed for rapid purification of unchelated metal ions and unbound DTPA. Colloidal stability was assessed with dynamic light scattering (DLS). Labeled MSNs suspensions were injected i.v. in mice, and scanned in dynamic MRI and in dynamic PET, followed by static scan acquisitions at time points. This study is a first step toward the pharmacokinetic modeling of MSN drug delivery.