Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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

Similar articles

  • Facile preparation of a new gadofullerene-based magnetic resonance imaging contrast agent with high 1H relaxivity.
    Shu C, Corwin FD, Zhang J, Chen Z, Reid JE, Sun M, Xu W, Sim JH, Wang C, Fatouros PP, Esker AR, Gibson HW, Dorn HC. Shu C, et al. Bioconjug Chem. 2009 Jun;20(6):1186-93. doi: 10.1021/bc900051d. Bioconjug Chem. 2009. PMID: 19445504 Free PMC article.
  • Gd3N@C84(OH)x: a new egg-shaped metallofullerene magnetic resonance imaging contrast agent.
    Zhang J, Ye Y, Chen Y, Pregot C, Li T, Balasubramaniam S, Hobart DB, Zhang Y, Wi S, Davis RM, Madsen LA, Morris JR, LaConte SM, Yee GT, Dorn HC. Zhang J, et al. J Am Chem Soc. 2014 Feb 12;136(6):2630-6. doi: 10.1021/ja412254k. Epub 2014 Feb 3. J Am Chem Soc. 2014. PMID: 24432974
  • Tri-gadolinium nitride PEGylated-hydroxylated endohedral metallofullerene.
    Zhang H. Zhang H. 2008 Oct 28 [updated 2008 Dec 1]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. 2008 Oct 28 [updated 2008 Dec 1]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. PMID: 20641442 Free Books & Documents. Review.
  • Water-soluble gadofullerenes: toward high-relaxivity, pH-responsive MRI contrast agents.
    Tóth E, Bolskar RD, Borel A, González G, Helm L, Merbach AE, Sitharaman B, Wilson LJ. Tóth E, et al. J Am Chem Soc. 2005 Jan 19;127(2):799-805. doi: 10.1021/ja044688h. J Am Chem Soc. 2005. PMID: 15643906
  • Gd@C82 Fullerenol.
    Zhang H. Zhang H. 2008 Oct 31 [updated 2008 Dec 1]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. 2008 Oct 31 [updated 2008 Dec 1]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. PMID: 20641737 Free Books & Documents. Review.
See all similar articles

Cited by

See all "Cited by" articles

References

    1. Caravan P, Ellison JJ, McMurry TJ, Lauffer RB. Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chem Rev. 1999;99:2293–2352. - PubMed
    1. Lauffer RB. Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging: Theory and Design. Chem Rev. 1987;87:901–927.
    1. Sieber MA, Pietsch H, Walter J, Haider W, Frenzel T, Weinmann HJ. A preclinical study to investigate the development of nephrogenic systemic fibrosis: A possible role for gadolinium-based contrast media. Invest Radiol. 2008;43:65–75. - PubMed
    1. Grobner T. Gadolinium - a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol, Dial, Transplant. 2006;21:1104–1108. - PubMed
    1. Shu CY, Zhang EY, Xiang JF, Zhu CF, Wang CR, Pei XL, Han HB. Aggregation studies of the water-soluble gadofullerene magnetic resonance imaging contrast agent: [Gd@C82O6(OH)16(NHCH2CH2COOH)8]x. J Phys Chem B. 2006;110:15597–15601. - PubMed

Publication types

MeSH terms