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In Vivo Tracking of Liposomes Using CT and MR Imaging

J. Zheng, J. Liu, D.A. Jaffray and C. Allen
University of Toronto, CA

Keywords:
liposome, computed tomography, magnetic resonance imaging, pharmacokinetics, contrast agent

Abstract:
Currently, there are limited methods available for longitudinal and non-invasive in vivo assessment of the transport kinetics of carrier-based therapeutics, such as those relying on liposomes. A viable strategy to non-invasively track the carrier in vivo is to employ the same carrier loaded with contrast-enhancing agents such as iodine and gadolinium. If these agents are retained within the carrier, they may act as surrogates for therapeutic molecules and allow for non-invasive tracking of the carrier in vivo using computed tomography (CT) and magnetic resonance (MR) imaging devices. If a correlation can be found between the change in signal intensities measured with CT and/or MR and the actual agent concentration detected in vivo, then this method has the potential to be successfully adopted for non-invasive quantification of pharmacokinetics and biodistribution studies. In this way, not only can the same animal be sampled over multiple time points, avoiding animal-to-animal variations, but the total number of animals required for each study can also be drastically reduced. Specifically, this study evaluated the in vivo pharmacokinetics, in both mice and rabbits, of a liposome-based CT and MR contrast agent previously developed by our research group. Correlations were established between the iodine and gadolinium concentrations found in the rabbit plasma by HPLC and ICP assays and the signal enhancement obtained in the rabbit aorta in CT and MR using circular regions of interest over all time points. A linear relationship was found between the iodine concentration and Hounsfield Unit increase in CT, while an exponential relationship was observed between the gadolinium concentration and signal intensity increase in MR. This pilot study demonstrated the potential of employing CT and MR imaging for longitudinal in vivo mapping of contrast agent containing liposomes.

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