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Gadolinium-Diethylenetriamine pentaacetic acid-poly(lactic-co-glycolic acid) microbubbles.


Leung K.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 Oct 11 [updated 2010 Dec 09].


Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used to create images because of their abundance in water molecules, which comprise >80% of most soft tissues. The contrast of proton MRI images depends mainly on the density of nuclear proton spins, the relaxation times of the nuclear magnetization (T1, longitudinal; T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the T1 and T2 relaxation times of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide and other iron oxide formulations affect T2 primarily and lead to a decreased signal. On the other hand, paramagnetic T1 agents such as gadolinium (Gd3+) and manganese (Mn2+) accelerate T1 relaxation and lead to brighter contrast images. Ultrasound is the most widely used imaging modality in clinical medicine (2) and its role in noninvasive molecular imaging is expanding with ligand-carrying microbubbles (3). Microbubbles are spherical cavities filled by a gas and encapsulated in a shell. The shells are made of phospholipids, surfactant, denatured human serum albumin, or synthetic polymer. Ligands and antibodies can be incorporated into the shell surface of microbubbles. Microbubbles are usually 1–8 μm in size and provide a strongly reflective interface and resonate to ultrasound waves. They are used as ultrasound contrast agents in imaging of inflammation, angiogenesis, intravascular thrombus, and tumors (4-6). They can also potentially be used for drug and gene delivery (7). Ao et al. (8) used poly(lactic-co-glycolic acid) (PLGA) as an encapsulating agent to form a multimodality imaging agent composed of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) (for MRI) and fluorocarbon-filled microbubbles (for ultrasound). Gd-DTPA-PLGA has been evaluated with in vivo imaging of the liver in rabbits, exhibiting enhanced MRI and ultrasound signals.

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