Kinetics of avidin‐induced clearance of biotinylated bimodal liposomes for improved MR molecular imaging

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Abstract
Dual labeled liposomes, carrying both paramagnetic and fluorescent lipids, were recently proposed as potent contrast agents for MR molecular imaging. These nanoparticles are coated with poly(ethylene glycol) (PEG) to increase their blood circulation half-life, which should allow extensive accumulation at the targeted site. To eliminate nonspecific blood pool signal from the MR images, the circulating liposomes should ideally be cleared from the circulation when sufficient target-specific contrast enhancement is obtained. To that aim, we designed an avidin chase that allowed controlled and rapid clearance of paramagnetic biotinylated liposomes from the blood circulation in C57BL/6 mice. Avidin-induced alterations in blood clearance kinetics and tissue distribution were studied quantitatively by determination of the Gd content in blood and tissue samples ex vivo. Intrinsic liposomal blood clearance showed bi-exponential behavior with half-lives t1/2α = 2.1 ± 1.1 and t1/2β = 15.1 ± 5.4 hours, respectively. In contrast, the contrast agent was cleared from the blood by the avidin infusion to 1-weighted MRI. The ability to rapidly clear circulating contrast agents opens up exciting possibilities to study targeting kinetics, to increase the specificity of molecular MRI and to optimize nanoparticulate contrast agent formulations. Magn Reson Med 60:1444–1456, 2008.
Funding Information
  • BSIK program entitled Molecular Imaging of Ischemic Heart Disease (project number BSIK03033)
  • EC-FP6-project DiMI (LSHB-CT-2005-512146)