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13:21
Preparation, Purification, and Characterization of Lanthanide Complexes for Use as Contrast Agents for Magnetic Resonance Imaging
Published on: July 21, 2011
High relaxivity trimetallic nitride (Gd3N) metallofullerene MRI contrast agents with optimized functionality
Jianfei Zhang1, Panos P Fatouros, Chunying Shu
1Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24060, USA.
Bioconjugate Chemistry
|March 12, 2010
Summary
New gadolinium nitride metallofullerene MRI contrast agents functionalized with poly(ethylene glycol) show high relaxivity. Optimized derivatives demonstrate potential for brachytherapy applications in brain tumors.
Area of Science:
- Nanotechnology
- Materials Science
- Radiochemistry
Background:
- Endohedral metallofullerenes offer unique properties for biomedical applications.
- Gadolinium-based agents are widely used for MRI contrast enhancement.
- Poly(ethylene glycol) (PEG) functionalization improves water solubility and biocompatibility.
Purpose of the Study:
- To synthesize and characterize water-soluble Gd(3)N@C(80)[DiPEG(OH)(x)] derivatives.
- To evaluate their performance as MRI contrast agents across various magnetic field strengths.
- To assess their potential for targeted drug delivery and brachytherapy.
Main Methods:
- Synthesis and characterization of Gd(3)N@C(80)[DiPEG(OH)(x)] derivatives with varying PEG molecular weights.
- Measurement of (1)H MRI relaxivities (r1 and r2) in aqueous solutions at 0.35, 2.4, and 9.4 T.
- Dynamic light scattering for size analysis and in vivo studies in tumor-bearing rats.
Main Results:
- Gd(3)N@C(80)[DiPEG(OH)(x)] derivatives exhibited high proton MRI relaxivities, particularly the 350/750 Da PEG variants (r1=237/232 mM(-1)s(-1), r2=460/398 mM(-1)s(-1) at 2.4 T).
- Relaxivities comparable to or exceeding current commercial and investigational MRI contrast agents were observed.
- Dynamic light scattering indicated larger particle sizes for 350/750 Da PEG derivatives (95/96 nm) versus 5000 Da (37 nm).
- In vivo studies in rats showed uniform distribution of 350 Da PEG derivatives in brain tumors, suggesting brachytherapy potential.
Conclusions:
- Water-soluble PEGylated Gd(3)N@C(80)[DiPEG(OH)(x)] derivatives are promising MRI contrast agents with high relaxivity.
- Optimized derivatives show potential for targeted delivery and theranostic applications, including brachytherapy, upon replacement with radionuclides like (177)Lu.
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