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Liposomal-based gadolinium Gd nanoparticles have elicited significant interest for use as blood pool and molecular magnetic resonance imaging MRI contrast agents. Previous generations of liposomal MR agents contained gadolinium-chelates either within the interior of liposomes core-encapsulated gadolinium liposomes or presented on the surface of liposomes surface-conjugated gadolinium liposomes. We hypothesized that a liposomal agent that contained both core-encapsulated gadolinium and surface-conjugated gadolinium, defined herein as dual-mode gadolinium Dual-Gd liposomes, would result in a significant improvement in nanoparticle-based T1 relaxivity over the previous generations of liposomal agents. In this study, we have developed and tested, both in vitro and in vivo, such a dual-mode liposomal-based gadolinium contrast agent.

Methodology-Principal Findings

Three types of liposomal agents were fabricated: core-encapsulated, surface-conjugated and dual-mode gadolinium liposomes. In vitro physico-chemical characterizations of the agents were performed to determine particle size and elemental composition. Gadolinium-based and nanoparticle-based T1 relaxivities of various agents were determined in bovine plasma. Subsequently, the agents were tested in vivo for contrast-enhanced magnetic resonance angiography CE-MRA studies. Characterization of the agents demonstrated the highest gadolinium atoms per nanoparticle for Dual-Gd liposomes. In vitro, surface-conjugated gadolinium liposomes demonstrated the highest T1 relaxivity on a gadolinium-basis. However, Dual-Gd liposomes demonstrated the highest T1 relaxivity on a nanoparticle-basis. In vivo, Dual-Gd liposomes resulted in the highest signal-to-noise ratio SNR and contrast-to-noise ratio in CE-MRA studies.


The dual-mode gadolinium liposomal contrast agent demonstrated higher particle-based T1 relaxivity, both in vitro and in vivo, compared to either the core-encapsulated or the surface-conjugated liposomal agent. The dual-mode gadolinium liposomes could enable reduced particle dose for use in CE-MRA and increased contrast sensitivity for use in molecular imaging.

Autor: Ketan B. Ghaghada, Murali Ravoori, Divya Sabapathy, James Bankson, Vikas Kundra , Ananth Annapragada



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