Contrast agents for MRI (original) (raw)
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Nano Liposomes Labeled with (99m)Tc-HMPAO, a Novel Agent for Blood Pool Imaging
Iranian journal of pharmaceutical research : IJPR, 2015
In-vitro labeling of RBC with (99m)Tc is an intricate procedure and there is always a need for an alternate blood pool imaging agent. The aim of this study was to prepare an effective nano sized liposome (NLs) similar to human RBC for blood pool scintigraphy. This study formulates PEG-NLs and non-PEG-NLs using film method plus high pressure homogenization technique. Biodistribution studies were performed on BALB/C mice 1, 4 and 24 h after tail vein injection of labeled NLs with (99m)Tc hexamethylpropylene-amine-oxime ((99m)Tc-HMPAO). Planar images were acquired using a 256 × 256 matrix following(99m) Tc-HMPAO-NLs injection into ear vein of rabbits 1, 2 and 24 h later. SPECT images were obtained 15 minutes after the injection (64 slices, 30 second/projection). The mean diameter, zeta potential and polydispersity index (PDI) of the PEG-NLs and the NLs were (80.88 ± 0.594 nm, -12.5 ± 0.56 mv, 0.158 ± 0.025) and (94.14 ± 0.114 nm, -35.5 ± 0.67 mv and 0.198 ± 0.007), respectively. (99m)T...
Liposomes containing paramagnetic macromolecules as MRI contrast agents
Magnetic Resonance in Medicine, 1986
The use of paramagnetic ions, bound to macromolecules and trapped in liposomes, as MRI contrast agents is suggested. As an example, the system of Mn2+ bound to serum proteins was tested. The binding of the metal ions to the macromolecules enhances their relaxation and at the same time decreases their rate of difision out of the liposomes. The use of liposomes is expected to reduce the potential toxicity of the paramagnetic ions and dows their targeting toward specific tissues. 0 1986 Academic Press, Inc.
pH-sensitive paramagnetic liposomes for MRI: assessment of stability in blood
Magnetic Resonance Imaging, 2003
The pH-dependent stability of dipalmitoyl phosphatidyl ethanolamine/palmitic acid (DPPE/PA) liposomal GdDTPA-BMA was investigated in human blood and after exposure to selected blood components. Relaxometry, visual observations and cryo-transmission electron microscopy (cryo-TEM) were employed for the assessment of stability. The liposomes were stable in buffer at physiological pH and the T 1 -relaxivity (r 1 ) of the system was significantly lowered compared to that of non-liposomal GdDTPA-BMA, which could be explained by an exchange limited relaxation process. Lowering the pH, however, gave a marked increase in r 1 , due to liposome aggregation and subsequent leakage of GdDTPA-BMA. After a few minutes incubation in human blood the liposomes were destabilised and leaky at both high and low pH, and blood components likely to cause the instability were studied. Physiological level of Na ϩ (150 mM) did not affect the relaxometric behavior of the liposomes at pH 7.4, but shifted the pH-r 1 profile laterally to higher pH-values compared to a level of 50 mM Na ϩ . Increased screening of the surface charges and, concomitantly, a lowering of the energy-barrier against aggregation is a plausible explanation for this phenomenon. In contrast, both Ca 2ϩ and Mg 2ϩ (physiological level, both 2 mM) caused massive aggregation of the liposomes and leakage of contents, and were therefore much more detrimental to the stability of the liposomes than a physiological level of Na ϩ . This could be due to the higher screening ability of divalent cations, but aggregation could also be induced through an inter-liposomal "bridging" effect. Physiological level of both Na ϩ and Ca 2ϩ caused less leakage than for lower Na ϩ concentration (50 mM Na ϩ and 2 mM Ca 2ϩ ), probably due to competition for the negative surface charges. Albumin also destabilised the liposomes, and it was shown to be due to an interaction between albumin and PA in the liposomal membrane.
Chemical Communications, 2014
A highly efficient contrast agent for magnetic resonance imaging was developed by encapsulating gadolinium within a stabilized porous liposome. The highly porous membrane leads to a high relaxivity of the encapsulated Gd. The stability of the liposome was improved by forming a polymer network within the bilayer membrane. Magnetic resonance imaging (MRI) procedures have become common practice in diagnostic clinical medicine, due to their ability to acquire high-resolution three-dimensional images of soft tissue and the absence of ionizing radiation. Many of these diagnostic procedures utilize intravenous MR contrast agents, such as gadolinium (Gd), to improve tissue contrast by shortening the longitudinal relaxation time (T1) of surrounding water protons. 1, 2 Most Gdbased MR contrast agents are small, non-targeted compounds that passively distribute into the intravascular and interstitial space with broad non-specific biodistribution. 2 In order to compensate for the low signal enhancement generated by individual Gd ions, most targeted Gd compounds have relied on the development of nanoplatforms that can carry a high payload of chelated Gd and which exhibit high longitudinal relaxivities (r1). 3-10 Currently, a wide range of nanoparticulate platforms including dendrimers, 11 liposomes, 12 polymersomes, 13, 14 micelles, 15 emulsions, 16 and silica nanoparticles, 16 have been tested as platforms for Gd labeling. For these MR contrast agents, it is not only the relaxivity per Gd that defines the effectiveness of the contrast agent but also the number of chelated Gd per nanoparticle. These two parameters can be represented as the relaxivity per nanoparticle. 17 Among the many nanoparticulate systems, phospholipid liposomes are particularly attractive due to the recognized and tested biocompatibility of many phospholipids as well as the increased functionality imparted by their amphiphilic structure. Specifically, hydrophilic drugs can be loaded in the aqueous lumen of the nanovesicles, whereas the hydrophobic domain serves as a natural carrier environment for hydrophobic drugs and the exterior surface can be functionalized with molecularly specific targeting ligands. Liposome-based drugs, Doxil (Janssen Biotech) have already been approved by the US Food and Drug Administration (FDA) for cancer treatment.
Liposome delivery of NMR contrast agents for improved tissue imaging
Magnetic Resonance in Medicine, 1986
Large unilamellar liposomes containing the paramagnetic contrast agent manganese chloride were shown to selectively enhance the intensity of the proton NMR signal from the livers of experimental mice. The kinetics ofthe observed effect indicate that the liposomes are rapidly removed from the circulation and deposited in high concentration within the liver. This process is known to involve the phagocytic activity of macrophages. These results show that liposomes could provide a useful and efficient vehicle for delivering NMR contrast agents to organs like the liver, spleen, and bone marrow. It may also be possible to use liposomes to selectively deliver contrast agents to tissue regions of developing pathology that are rich in macrophage activity.
New applications of nanoparticles in cardiovascular imaging
Journal of Experimental Nanoscience, 2007
Nanotechnology involves working at the atomic, molecular, and macromolecular levels including imaging. Recently, four areas have emerged in cardiovascular imaging: 1.Targeted therapeutics to deliver cardioprotective drugs where they are needed; 2. Myocardial tissue engineering to replace defective valves, damaged heart muscle, clogged blood vessels; 3. Molecular imaging using "smart" imaging agents in targeted therapeutics and imaging; 4.Biosensors and myocardial diagnostics. Several approaches of nanoparticles i.e. dendrimers, liposomes, polymer delivery molecules, cantilevers, nanoscaffolds, nanofibers are potential candidates in cardiac visualization. The extracellular matrix plays significant role by chemokines, cytokines and growth factors. The limitations of these emerging techniques and a new possibility of MRI visualization of mice cardiac atheroma by superparamagnetic iron-oxide gadolinium-apoferritin (SPIOA), myoglobin (SPIOM), for targeted functional and molecular imaging of atherosclerosis are main focus of this paper. These emerging techniques provide opportunity of tracking functional and structural changes in myocardium and heart tissue.
Determination of water permeability of paramagnetic liposomes of interest in MRI field
Journal of Inorganic Biochemistry, 2008
The water permeability of various liposome membranes has been determined at 298 K by measuring the NMR longitudinal water proton relaxation rate of vesicles encapsulating the clinically approved Gd-HPDO3A complex (HPDO3A = 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid). Two basic formulations based on DPPC (dipalmitoylphosphatidylcholine) and POPC (palmitoyl-oleylphosphatidylcholine) phospholipids were selected and investigated. Furthermore, the permeability changes caused by the membrane incorporation of amphiphiles like cholesterol and/or metal complexes of interest for designing improved liposomebased MRI contrast agents, were also investigated. The incorporation of cholesterol and metal complexes bearing C18 saturated chains in POPC-based liposomes reduces the water diffusivity across the membrane bilayer. On the contrary, the incorporation of a macrocyclic metal complex bearing four C12 alkylic chains, one for each coordination arm of the ligand, considerably enhances the water permeability in DPPC-based liposomes. Finally, it is reported that the permeability of POPC-based bilayer is increased when the liposomes are subjected to an osmotic stress.