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Gd‐DTPA‐Dopamine‐Bisphytanyl Amphiphile: Synthesis,Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents
Authors:Abhishek Gupta  Dr Scott A Willis  Lynne J Waddington  Dr Tim Stait‐Gardner  Dr Liliana de Campo  Prof Dennis W Hwang  Dr Nigel Kirby  Prof William S Price  Dr Minoo J Moghaddam
Affiliation:1. Manufacturing Flagship CSIRO, P.O. Box 52, North Ryde, NSW, 1670 (Australia);2. Nanoscale Organisation and Dynamics Group, University of Western Sydney, Penrith, NSW, 2751 (Australia);3. Manufacturing Flagship CSIRO, 343 Royal Parade, Parkville, VIC, 3052 (Australia);4. Bragg Institute ANSTO, Lucas Heights, NSW, 2234 (Australia);5. Department of Chemistry and Biochemistry, National Chung Cheng University, Min‐Hsiung Township Chiayi, 621 (Taiwan);6. Australian Synchrotron, 800 Blackburn Road, Clayton, VIC, 3168 (Australia)
Abstract:Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a GdIII‐chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd‐DTPA‐dopamine‐bisphytanyl (Gd‐DTPA‐Dop‐Phy), which is readily capable of self‐assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.40 T. Analysis of variable temperature 17O NMR transverse relaxation measurements revealed the water exchange of the nanoassemblies to be faster than that previously reported for paramagnetic liposomes. Molecular reorientation dynamics were probed by 1H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari–Szabo “model‐free” approach. High payloads of GdIII ions in the liposomal nanoassemblies made solely from the Gd‐DTPA‐Dop‐Phy amphiphiles, in combination with slow molecular reorientation and fast water exchange makes this novel amphiphile a suitable candidate to be investigated as an advanced MRI contrast agent.
Keywords:contrast agents  gadolinium‐DTPA‐amphiphiles  liposomes  17O   NMR spectroscopy  relaxation
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