In vivo tracking of liposomes using CT and MR imaging

There are limited methods that are currently 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 liposomes in vivo is to load them with contrast-enhancing agents that are well retained within the carrier. The encapsulation of contrast agents such as iodine and gadolinium allows for the liposomes to be tracked by computed tomography (CT) and magnetic resonance (MR) imaging systems, respectively. This study evaluated the feasibility of using CT and MR imaging as a means to gain a quantitative assessment of the pathway and fate of liposomes in vivo in rabbits. The liposome formulation examined was composed of DPPC/Cholesterol/DSPE-PEG₂₀₀₀ in a 55/40/5 molar ratio and the vesicles had an average diameter of 80 nm. The commercially available agents iohexol (CT agent) and gadoteridol (MR agent) were encapsulated within the liposomes and found to be retained over a 15-day period in vitro. Following i.v. administration of the CT and MR agent-containing liposomes the relative signal intensities in both imaging modalities were monitored over a 7-day period. The signal intensities were then compared with the values obtained for the concentration of each agent present in blood as measured by HPLC and ICP-AES analyses. Overall, the values obtained for the amount of agent in blood using non-invasive imaging correlated well with that measured using the traditional analytical techniques (R²=0.9). This pilot study demonstrated the potential of employing CT and MR imaging for longitudinal in vivo mapping of liposomes and other nano-sized carriers.