Long-circulating liposomal contrast agents for magnetic resonance imaging.
Contrast-enhanced magnetic resonance imaging (CE-MRI) is a dynamic technique for imaging vasculature. However, the currently used gadolinium (Gd) chelates, such as Gd-DTPA, restrict the time window for image acquisition due to their rapid elimination from blood and their rapid diffusion into the extravascular space, which prevents their use in steady-state imaging, particularly for MR angiography (MRA). The goal of this study was to prepare long-circulating polyethylene glycol-bearing ((PEG)ylated) liposomes encapsulating Gd chelate, and characterize and demonstrate their utility for MRA. The liposomes were prepared by hydrating a mixture of lipids with gadodiamide (Omniscan). The liposomes were sized down to around 100 nm by extruder and exhaustively dialysed to remove the unencapsulated gadodiamide. The Gd liposomes exhibited a significant sustained (>4 hr) contrast enhancement of the vasculature with improved spatial details in a rat model with little leakage relative to Gd-DTPA controls as shown by MRI. We suggest that such long-circulating liposomal formulations allow for high spatial resolution imaging without the confounding effects of clearance and extravascular diffusion of the agent complicating the data and image analysis.
WHC Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, Georgia 30332-0535, USA.
Ananta Laxmi
AL
Ayyagari
Xiaodong
X
Zhang
Ketan B
KB
Ghaghada
Ananth
A
Annapragada
Xiaoping
X
Hu
Ravi V
RV
Bellamkonda
D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000737:chemistry*; D007089:Image Enhancement / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods; D008081:Liposomes; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors
D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D008081:Liposomes; D011092:Polyethylene Glycols; D019786:Gadolinium DTPA