Paramagnetic Polymerized Liposomes: Synthesis, Characterization, and Applications for Magnetic Resonance Imaging

Storrs, Richard W.; Tropper, François D.; Li, Henry Y.; Song, Curtis K.; Kuniyoshi, Jeremy K.; Sipkins, Dorothy A.; Li, King C.; Bednarski, Mark D.

doi:10.1021/ja00133a001

Cited by 94 publications

(58 citation statements)

References 2 publications

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“…This could be due to the presence of PEG chains in sample D that influence the exchange lifetime (t M ) of the metal-coordinated water molecule of the Gd-complex in the aggregated forms. [29] In fact, the t M values, as determined by 17 O NMR experiments, were longer for sample D (t M = 474 ns) than sample E (t M = 81 ns).…”

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confidence: 90%

Peptide Derivatized Lamellar Aggregates as Target‐Specific MRI Contrast Agents

et al. 2007

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The relaxivity behaviour and the structural characterization of new supramolecular aggregates (bilayer structures and micelles) obtained by combining two different amphiphilic monomers are reported. One monomer, (C18)(2)DTPAGlu-Gd, contains a very stable gadolinium complex, and the other, DSPE-PEG(2000)-CCK8, contains the bioactive CCK8 peptide. Samples that contained only DSPE-PEG(2000)-CCK8, or up to 50 % (C18)(2)DTPAGlu-Gd, aggregated as double-layer structures (lamellar aggregates) with a thickness of approximately 80-100 A, as evaluated by SANS measurement and Cryo-TEM imaging. A transition to micelle formation was observed when the amount of (C18)(2)DTPAGlu-Gd in the aggregate was increased. These were rod-like micelles approximately 40 A in radius and >200 A in length. The proton relaxivities for both lamellar aggregates and rod-like micelles were the same (17.2 mM(-1) s(-1)), although the values were the results of different combinations of local and global contributions. The in vitro target selectivity of aggregates that contained the CCK-8 peptide was demonstrated by using nuclear medicine techniques.

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confidence: 90%

Peptide Derivatized Lamellar Aggregates as Target‐Specific MRI Contrast Agents

et al. 2007

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“…We have investigated particles with metal chelators such as DTPA attached to the surface and a particle synthesis approach based on self-assembly followed by rapid screening for polymerized vesicles (PVs) that efficiently bind to receptors and other cell surface molecules useful for imaging. Our technology uses a chelator with metal attached to the monomers prior to particle construction, as we have previously described (19,20). PVs with the desired metal affinity can be conjugated to targeting agents such as the monoclonal antibody, LM609 (Chemicon), to confer the specificity for endothelial cell receptors via a biotin avidin bridge.…”

Section: Pv Synthesis and Characterizationmentioning

confidence: 99%

“…PVs were formed by combining base lipids such as compound 3 with 29% of the chelating lipids containing Gd(ϩ3) ions such as compound 2, and to 1% of the biotinylated monomer 1 for antibody conjugation. Formation of PVs was accomplished by using a dispersion-extrusion technique followed by photopolymerization with UV light (254 nm), as previously described (19,20).…”

Section: Pv Synthesis and Characterizationmentioning

confidence: 99%

“…However, in order to optimize the target to background ratio, a delivery vehicle has to be designed to have the following characteristics: 1) sufficiently long intravascular halflife to allow the agents to interact and accumulate at the target site, 2) multivalency to increase affinity and avidity to the molecular targets, 3) capacity to carry a high payload of contrast or therapeutic agents since receptor density may not be very high, 4) ability to accept different targeting ligands, contrast and therapeutic agents with minimal modification, and 5) non-toxic and well tolerated. Our approach is to use polymerized vesicles (PVs) (19,20) which are designed to have all the necessary characteristics required for vascular targeted imaging and therapy.…”

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Vascular‐targeted molecular imaging using functionalized polymerized vesicles

Bednarski

2002

Magnetic Resonance Imaging

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In this review we will discuss the use of multivalent polymerized vesicles (PVs) combined with magnetic resonance imaging (MRI) and gamma scintigraphy to image expression of vascular molecular receptors in vivo. Specifically, we will present our data on the use of this technology to design imaging agents toward specific vascular receptors in both a mouse and rabbit tumor model and in the EAE mouse, a model for human multiple sclerosis (MS). Examples will be shown where the in vivo specificity of the targeted molecular imaging agents was validated in the animal models. Since the PVs are designed to carry either contrast or therapeutic agents or both, we can potentially use vascular-targeted imaging for selecting patients and guiding vascular-targeted therapies in these patients. Using this combined vascular-targeted imaging and therapy approach, personalized treatment can potentially be delivered, maximizing efficacy and minimizing side effects.

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“…The introduction of MR-based molecular imaging (3) revived the exploitation of paramagnetic liposomes, albeit, for this purpose, functionalization with targeting ligands is a prerequisite (4). Mark Bednarski and colleagues introduced a polymerizable liposomal contrast agent (5), and were the first to show molecular MRI of angiogenesis in a rabbit model in 1998 (6). An overview of developments in, and the current status of, paramagnetic liposomes can be found in the opening review paper of the current issue by Nicolay and coworkers (7).…”

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confidence: 99%