Cellular compartmentalization of internalized paramagnetic liposomes strongly influences both T₁ and T₂ relaxivity

Abstract

In recent years, numerous Gd 3؉ -based contrast agents have been developed to enable target-specific MR imaging of in vivo processes at the molecular level. The combination of powerful contrast agents and amplification strategies, aimed at increasing the contrast agent dose at the target site, is an often-used strategy to improve the sensitivity of biomarker detection. One such amplification mechanism is to target a disease-specific cell membrane receptor that can undergo multiple rounds of internalization following ligand binding and thus shuttle a sizeable amount of contrast agent into the target cell. An example of such a membrane receptor is the ␣ ␤ 3 integrin. The goal of this study was to investigate the consequences of this amplification approach for the T 1 -and T 2 -shortening efficacy of a paramagnetic contrast agent. Cultured endothelial cells were incubated with paramagnetic liposomes that were conjugated with a cyclic RGD-peptide to enable internalization by means of the ␣ ␤ 3 integrin receptor. Non-targeted liposomes served as a control. This study showed that ␣ ␤ 3 targeting dramatically increased the uptake of paramagnetic liposomes. This targeting strategy, however, strongly influenced both the longitudinal and transverse relaxivity of the internalized paramagnetic liposomes. Magn Reson Med 61:1022-1032, 2009.

Cationic Gd-DTPA Liposomes for Highly Efficient Labeling of Mesenchymal Stem Cells and Cell Tracking with MRI

“…Viability was (SE) images, the least cell concentration that could be checked prior to injection, showing 98% of cells to be the cationic liposomes. With a different liposome formulation, in a recent study (28) no statistically significant nonviable. Nonviable cells showed a remarkable hyperenhancement, immediately after injection (Fig.…”

“…More recently, Gd chelates have been receiving Liposome solutions were extruded at 45°C through a increasing interest as an intracellular imaging probe high-pressure Lipex thermoline extruder (Northern Lipids (1,4,15,28,53). One of the main advantages of Gd cheInc, Vancouver, Canada) by sequential passing through lates over T2 CAs is their predominant positive contrast Nuclepore polycarbonate membrane filters (Whatman, effect due to T1 shortening.…”

“…The rationale behind making them cationic was resultant size of different batches of Gd-DTPA lipoto improve uptake by binding to anionic charges in the somes as determined by DLS was 111-123 nm with a cell membrane. Liposomes have already widely been polydispersity index (PDI) of 0.04-0.09, whereas used for both diagnostic (16,28,35) and therapeutic pur-HEPES control liposomes were slightly larger with sizes poses (2,30,47) or combinations thereof (29) and are a 114-129 nm (PDI 0.06-0.12). The zeta potential was well-known vehicle in DNA transfection studies (24, 43 ± 7.0 mV.…”

Molecular Imaging in Cardiovascular Diseases

“…Depending upon the composition of the contrast medium or molecular probe, the relaxation effect additionally varies with the strength of the external magnetic field. An important factor in this depends upon whether the contrast medium is in the extracellular region, is bound to a receptor, or is absorbed intracellularly [31,32]. T1-shortening MR contrast agents can, for example, be synthesized through conjugation of small ligands (e. g. small molecules, peptides, antibodies or glucose) with gadolinium chelate.…”

Lipid-Based Nanoparticles in Cardiovascular Molecular Imaging

“…In fact, the liposome intracellular distribution in vesicles can limit the attainable relaxation enhancement as a consequence of the reduced water exchange across the barriers among the different compartments. [38][39][40]. On the contrary, changes in fluorescence measurements are typically linear over the ranges studied.…”