Dual mode gadolinium nanoparticle contrast agents
OwnerVikas Kundra, James A. Bankson +3inventors
InventorsVikas Kundra, James A. Bankson, Ananth Annapragada, Ketan B. Ghaghada, Murali K. Ravoori
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Abstract
Provided herein are nanoparticle-based gadolinium (Gd) agents which may be used, e.g., in T1-weighted MR imaging (MRI). In various embodiments, dual-Gd liposomal agents are provided which contain both core-encapsulated Gd as well as surface-conjugated Gd. In various embodiments, these agents were observed to deliver a higher concentrations of Gd and result in substantial improvements in signal to noise ratios and contrast to noise ratios. Also provided are methods for in vivo imaging and/or treating diseases such as cancer or tumor in a subject.
Claims33
An imaging nanoparticle comprising a liposome or micelle, wherein the liposome or micelle comprises a first T1 relaxation magnetic resonance imaging agent on the surface of the liposome or micelle and a second T1 relaxation magnetic resonance imaging agent that is encapsulated within the liposome or micelle;
- wherein the liposome or micelle is formulated for magnetic resonance imaging;
- wherein the nanoparticle comprises the first and second T1 relaxation magnetic resonance imaging agents in an amount that together result in an increase in the T1 relaxivity signal from 0.2 fold to 4 fold on a per nanoparticle basis, wherein the nanoparticle has a diameter of about 10-300 nm when the T1 relaxation signal is measured, and wherein the T1 relaxation signals are obtained by diluting in bovine plasma in vitro;
- wherein the increase in the T1 relaxivity signal on a per nanoparticle basis is relative to a corresponding liposome or micelle that contains either the same amount of the first T1 relaxation magnetic resonance imaging agent on the surface of the liposome or micelle or the same amount of the second T1 relaxation magnetic resonance imaging agent encapsulated within the liposome or micelle;
- wherein the first T1 relaxation magnetic resonance imaging agent is Gd-DTPA bis(stearylamide) (Gd-DTPA-BSA) and
- the second T1 relaxation magnetic resonance imaging agent is gadobenate dimeglumine (Gd-BOPTA)
- wherein the nanoparticle comprises dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (mPEG2000-DSPE);
- and
- wherein the nanoparticles have been formed by a method comprising mixing in ethanol, rehydrating, and extruding through a filter or membrane, wherein the filter or membrane has a plurality of openings about 10-400 nm in size;
- and
- wherein the rehydrating comprises exposing the nanoparticle to a solution comprising the second T1 relaxation magnetic resonance imaging agent.
Dependencies are inferred from the claim text.