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. 2010 Apr 21;21(4):610-5.
doi: 10.1021/bc900375n.

High relaxivity trimetallic nitride (Gd3N) metallofullerene MRI contrast agents with optimized functionality

Jianfei Zhang  1 , 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
Affiliations

High relaxivity trimetallic nitride (Gd3N) metallofullerene MRI contrast agents with optimized functionality

Jianfei Zhang et al. Bioconjug Chem. .

Abstract

Water-soluble poly(ethylene glycol) (PEG) functionalized and hydroxylated endohedral trimetallic nitride metallofullerene derivatives, Gd(3)N@C(80)[DiPEG(OH)(x)], have been synthesized and characterized. The (1)H 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 r(1) and 460/398 mM(-1) s(-1) for r(2) (79/77 mM(-1) s(-1) and 153/133 mM(-1) s(-1) based on Gd(3+) 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 Gd(3+) ions are replaced with radioactive (177)Lu.

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Figures

Figure 1
Figure 1
The Gd3N@C80[DiPEG(OH)x] nanoparticle with several hydrogen-bonded water molecules shown.
Figure 2
Figure 2
(a) 400MHz 1H NMR spectra of Gd3N@C80[DiPEG350(OH)x] (top) in comparison with DiPEGM350 malonate (bottom) in D2O; (b) UV-Vis spectra of Gd3N@C80 and Gd3N@C80[DiPEG2000(OH)x]. Note the disappearance of the characteristic peaks in the derivative at 330 and 410 nm.
Figure 3
Figure 3
Size distribution function of Gd3N@C80[DiPEG(OH)x] from DLS experiment. The mean peak position is 75nm, 76nm, 58nm and 37nm for Gd3N@C80[DiPEG350(OH)x], Gd3N@C80[DiPEG750(OH)x], Gd3N@C80[DiPEG2000(OH)x] and Gd3N@C80[DiPEG5000(OH)x] respectively.
Figure 4
Figure 4
T1 computed images and T1w image of a live rat brain after direct infusion into the tumor of 0.0235 mM Gd3N@C80[DiPEG350(OH)x].
See this image and copyright information in PMC

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