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In Vitro And In Vivo Imaging Studies Of A New Endohedral Metallofullerene Nanoparticle.

P. Fatouros, F. Corwin, Z. Chen, W. Broaddus, J. Tatum, B. Kettenmann, Zhongxin Ge, H. Gibson, J. L. Russ, A. P. Leonard, J. Duchamp, H. Dorn
Published 2006 · Medicine

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PURPOSE To evaluate the effectiveness of a functionalized trimetallic nitride endohedral metallofullerene nanoparticle as a magnetic resonance (MR) imaging proton relaxation agent and to follow its distribution for in vitro agarose gel infusions and in vivo infusions in rat brain. MATERIALS AND METHODS The animal study was approved by the animal care and use committee. Gd(3)N@C(80) was functionalized with poly(ethylene glycol) units, and the carbon cage was hydroxylated to provide improved water solubility and biodistribution. Relaxation rate measurements (R1 = 1/T1 and R2 = 1/T2) of water solutions of this contrast agent were conducted at 0.35-, 2.4-, and 9.4-T MR imaging. Images of contrast agent distributions were produced following infusions in six agarose gel samples at 2.4 T and from direct brain infusions into normal and tumor-bearing rat brain at 2.4 T. The relaxivity of a control functionalized lutetium agent, Lu(3)N@C(80), was also determined. RESULTS Water hydrogen MR imaging relaxivity (r1) for this metallofullerene nanoparticle was markedly higher than that for commercial agents (eg, gadodiamide); r1 values of 102, 143, and 32 L . mmol(-1) . sec(-1) were measured at 0.35, 2.4, and 9.4 T, respectively. In studies of in vitro agarose gel infusion, the use of functionalized Gd(3)N@C(80) at concentrations an order of magnitude lower resulted in equivalent visualization in comparison with commercial agents. Comparable contrast enhancement was obtained with direct infusions of 0.013 mmol/L of Gd(3)N@C(80) and 0.50 mmol/L of gadodiamide in live normal rat brain. Elapsed-time studies demonstrated lower diffusion rates for Gd(3)N@C(80) relative to gadodiamide in live normal rat brain tissue. Functionalized metallofullerenes directly infused into a tumor-bearing brain provided an improved tumor delineation in comparison with the intravenously injected conventional Gd(3+) chelate. A control lutetium functionalized Lu(3)N@C(80) nanoparticle exhibited very low MR imaging relaxivity. CONCLUSION The new functionalized trimetallic nitride endohedral metallofullerene species Gd(3)N@C(80)[DiPEG5000(OH)(x)] is an effective proton relaxation agent, as demonstrated with in vitro relaxivity and MR imaging studies, in infusion experiments with agarose gel and in vivo rat brain studies simulating clinical conditions of direct intraparenchymal drug delivery for the treatment of brain tumors.
This paper references
10.1021/NL025643M
Lutetium-based Trimetallic Nitride Endohedral Metallofullerenes: New Contrast Agents
Erick B. Iezzi (2002)
10.1021/JA055089T
Purification of endohedral trimetallic nitride fullerenes in a single, facile step.
Zhongxin Ge (2005)
10.1038/43415
Small-bandgap endohedral metallofullerenes in high yield and purity
S. Stevenson (1999)
10.1021/JA044688H
Water-soluble gadofullerenes: toward high-relaxivity, pH-responsive MRI contrast agents.
E. Tóth (2005)
10.1021/JA027555+
Lanthanoid endohedral metallofullerenols for MRI contrast agents.
H. Kato (2003)
10.1038/318162a0
C60: Buckminsterfullerene
H. W. Kroto (1985)
10.1021/BC000136M
Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents.
M. Mikawa (2001)
10.1002/1521-3765(20021004)8:19<4528::AID-CHEM4528>3.0.CO;2-8
Preparation and crystallographic characterization of a new endohedral, Lu3N@C80.5 (o-xylene), and comparison with Sc3N@C80.5 (o-xylene).
S. Stevenson (2002)
10.3171/JNS.2004.101.2.0314
A realistic brain tissue phantom for intraparenchymal infusion studies.
Z. Chen (2004)
10.1021/JA0340984
First soluble M@C60 derivatives provide enhanced access to metallofullerenes and permit in vivo evaluation of Gd@C60[C(COOH)2]10 as a MRI contrast agent.
R. D. Bolskar (2003)
10.1002/ANIE.200461441
Gadolinium nitride Gd3N in carbon cages: the influence of cluster size and bond strength.
M. Krause (2005)
10.2174/1389557013406684
Fullerenes in medicinal chemistry and their biological applications.
N. Tagmatarchis (2001)
10.1097/00006123-199207000-00013
Cerebrovascular effects and tumor kinetics after a single intratumoral injection of human recombinant interleukin-2 alone or in combination with intravenous chemotherapy in a rat model of glioma.
R. G. Watts (1992)
10.1021/AR970300U
PROTOTROPIC AND WATER-EXCHANGE PROCESSES IN AQUEOUS SOLUTIONS OF GD(III) CHELATES
S. Aime (1999)
10.1039/B413536A
Efficient relaxivity enhancement in dendritic gadolinium complexes: effective motional coupling in medium molecular weight conjugates.
D. A. Fulton (2005)
10.1109/10.821776
Determination of intracranial tumor volumes in a rodent brain using magnetic resonance imaging, Evans Blue, and histology: a comparative study
S. Prabhu (2000)
10.1021/JA00068A005
Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification
S. Friedman (1993)
10.1097/00005072-197507000-00004
THE INDUCTION OF INTRACRANIAL NEOPLASMS BY THE INOCULATION OF AVIAN SARCOMA VIRUS IN PERINATAL AND ADULT RATS
D. Copeland (1975)
Experimental chemotherapy of viral induced brain tumors
J. Swenberg (1974)
10.1109/10.979348
Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels
Z. Chen (2002)
10.1039/B412338G
Pyramidalization of Gd3N inside a C80 cage. The synthesis and structure of Gd3N@C80.
S. Stevenson (2004)
10.1073/PNAS.96.9.5182
In vivo studies of fullerene-based materials using endohedral metallofullerene radiotracers.
D. W. Cagle (1999)



This paper is referenced by
10.1039/c0cc03893h
14N and 45Sc NMR study of trimetallic nitride cluster (M3N)6+ dynamics inside a icosahedral C80 cage.
Wujun Fu (2011)
10.1166/JBN.2007.043
Gadofullerenes and Gadonanotubes: A New Paradigm for High-Performance Magnetic Resonance Imaging Contrast Agent Probes
B. Sitharaman (2007)
10.1021/cr500171e
Lutetium-177 therapeutic radiopharmaceuticals: linking chemistry, radiochemistry, and practical applications.
S. Banerjee (2015)
10.1016/J.JPCS.2019.109094
Electrophysical properties of hydroxylated endohedral metallofullerene with gadolinium
Alexander S. Dudnik (2019)
10.1007/978-1-4020-6845-4_1
Twenty Years of Promises: Fullerene in Medicinal Chemistry
T. Ros (2008)
10.1002/chem.201502511
Preparation, Structural Determination, and Characterization of Electronic Properties of Bis-silylated and Bis-germylated Lu3 N@Ih -C80.
M. Kako (2015)
10.1002/SLCT.201801038
Are Small Quasi‐Fullerenes Capable of Encapsulating Trimetallic Nitrides A3‐xBxN (A, B =Sc, Y, La, x=0‐3)? A DFT Study
Christian A Celaya (2018)
10.1021/acsami.7b04718
Trimetallic Nitride Endohedral Fullerenes Carboxyl-Gd3N@C80: A New Theranostic Agent for Combating Oxidative Stress and Resolving Inflammation.
T. Li (2017)
10.1186/1532-429X-15-7
Functionalization of gadolinium metallofullerenes for detecting atherosclerotic plaque lesions by cardiovascular magnetic resonance
A. Dellinger (2013)
10.1039/c1cc10123d
Chemistry of endohedral metallofullerenes: the role of metals.
X. Lu (2011)
10.1002/9780470660188.CH9
New Endohedral Metallofullerenes: Trimetallic Nitride Endohedral Fullerenes
Marilyn M Olmstead (2010)
w naukach biomedycznych* Fullerenol - properties and applications in biomedical sciences
Jacek Grębowski (2013)
Gadolinium Endohedral Metallofullerenes for Future Magnetic Resonance Imaging Contrast Agents
Youqing Ye (2014)
Preparation, Separation, Characterization and Hydrogenation of Endohedral Metallofullerenes
W. Fu (2009)
10.1039/c3dt53517g
Gadolinium-containing endohedral fullerenes: structures and function as magnetic resonance imaging (MRI) agents.
K. Ghiassi (2014)
Novel applications of nanotechnology in medicine.
A. Surendiran (2009)
10.1081/E-ENN3-120019119
Fullerenes: Magnetic Behavior
Tatiana L. Makarova (2014)
10.1021/jm800521j
Hydrochalarones: a novel endohedral metallofullerene platform for enhancing magnetic resonance imaging contrast.
D. Macfarland (2008)
10.1021/JP509975W
Facile Synthesis of an Extensive Family of Sc2O@C2n (n = 35–47) and Chemical Insight into the Smallest Member of Sc2O@C2(7892)–C70
Meirong Zhang (2014)
10.1039/c9nr04129j
The pharmaceutical multi-activity of metallofullerenol invigorates cancer therapy.
J. Li (2019)
10.2217/NNM.12.112
Iron oxide-based nanostructures for MRI and magnetic hyperthermia.
I. Hilger (2012)
10.1007/978-3-319-89878-0_12
Fullerenes for Cancer Therapy and Bioimaging
Xuejiao J. Gao (2018)
10.1002/wcms.21
Fullerenes: formation, stability, and reactivity
A. Rodríguez-Fortea (2011)
10.1039/c3cs60410a
Visualizing the atherosclerotic plaque: a chemical perspective.
Ma Teresa Albelda (2014)
10.1148/radiol.11102569
Metallofullerene-based nanoplatform for brain tumor brachytherapy and longitudinal imaging in a murine orthotopic xenograft model.
M. Shultz (2011)
10.1039/B706859J
Effect of copper metal on the yield of Sc3N@C80 metallofullerenes.
S. Stevenson (2007)
10.1021/JA3073929
Synthesis of silylene-bridged endohedral metallofullerene Lu3N@I(h)-C80.
Kumiko Sato (2012)
10.1016/J.CCR.2013.05.020
Endohedral metallofullerenes: An unconventional core–shell coordination union
H. Cong (2013)
10.4155/tde-2018-0022
Nanotechnology-based strategies as novel therapies in gliomas.
Puja S. Gaikwad (2018)
Carbon Nanoparticles in Aquatic Environments
Kukka Pakarinen (2013)
10.1021/ic5021884
Popular C82 fullerene cage encapsulating a divalent metal ion Sm(2+): structure and electrochemistry.
Ziqi Hu (2015)
10.1557/JMR.2016.449
30 years of advances in functionalization of carbon nanomaterials for biomedical applications: a practical review
Neelkanth M Bardhan (2017)
See more
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