High Relaxivity Trimetallic Nitride (Gd3N) Metallofullerene MRI Contrast Agents with Optimized Functionality

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• 作者：Jianfei Zhang ; Panos P. Fatouros ; Chunying Shu ; Jonathan Reid ; Lesley Shantell Owens ; Ting Cai ; Harry W. Gibson ; Gary L. Long ; Frank D. Corwin ; Zhi-Jian Chen ; Harry C. Dorn
• 刊名：Bioconjugate Chemistry
• 出版年：2010
• 出版时间：April 21, 2010
• 年：2010
• 卷：21
• 期：4
• 页码：610-615
• 全文大小：269K
• 年卷期：v.21,no.4(April 21, 2010)
• ISSN：1520-4812

文摘

Water-soluble poly(ethylene glycol) (PEG) functionalized and hydroxylated endohedral trimetallic nitride metallofullerene derivatives, Gd₃N@C₈₀[DiPEG(OH)_x], have been synthesized and characterized. The ¹H MRI relaxivities in aqueous solution were measured for the derivatives with four different molecular weights of PEG (350−5000 Da) at 0.35, 2.4, and 9.4 T. The 350/750 Da PEG derivatives have the highest relaxivities among the derivatives, 237/232 mM⁻¹ s⁻¹ for r₁ and 460/398 mM⁻¹ s⁻¹ for r₂ (79/77 mM⁻¹ s⁻¹ and 153/133 mM⁻¹ s⁻¹ based on Gd³⁺ ion), respectively, at a clinical-range magnetic field of 2.4 T. These represent some of the highest relaxivities reported for commercial or investigational MRI contrast agents. Dynamic light scattering results confirm a larger average size for 350/750 Da PEGs derivatives (95/96 nm) relative to longer chain length derivatives, 5000 Da PEG derivatives (37 nm). Direct infusion of the optimized 350 Da PEG derivatives into live tumor-bearing rat brains demonstrated an initial uniform distribution, and hence, the potential for effective brachytherapy applications when the encapsulated Gd³⁺ ions are replaced with radioactive ¹⁷⁷Lu.