Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing
Reexamination Certificate
2001-04-20
2002-10-29
Jones, Dameron L. (Department: 1616)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
C534S015000, C424S001110
Reexamination Certificate
active
06471942
ABSTRACT:
FIELD OF THE INVENTION
This application is related to imaging and treatment methods for a body. In particular, it relates to an imaging and treatment method which employs trimetallic nitride template endohedral metallofullerene compounds.
BACKGROUND OF THE INVENTION
Endohedral metallofullerenes are fullerene structures (carbon clusters) with closed topologies, encapsulating metallic or non-metallic atoms. Typically, metallofullerenes are prepared by impregnating graphite rods with a metal salt and annealing at approximately 1000° C. Before the rods bum, a small amount of metallofullerene is produced in the soot. The soot is then extracted with solvents such as CS
2
or o-dichlorobenzene, followed by high performance liquid chromatography (HPLC) to obtain pure samples of the endohedral metallofullerenes. M@C
82
is the most predominant species extracted. However, multiple metal-atom species such as Y, Ho, or Er dimers, and Sc trimer have also be formed and extracted. Although a broad range of endohedral species containing from 60 to 200 carbon atoms and one or more metal atoms have been formed, most are insoluble and, thus, are not useful for biological applications. Typical metal atoms that are encapsulated are alkali metal, alkaline earth metal, Sc, Y, U or a lanthanide metal. The lanthanide elements have been found to be useful for diagnostic and therapeutic medicine, making them attractive for applications in medicine.
Current synthesis methods make it difficult to perform detailed studies of the properties associated with endohedral metallofullerenes because the typical yields are less than 0.5%. In addition, multiple endohedral fullerene isomers are produced using these synthetic methods.
Stevenson et al. (“Small-bandgap endohedral metallofullerenes in high yield and purity,”
Nature
, Sep. 2, 1999, Vol. 401, pp. 55-57) describe a technique where the introduction of small amounts of nitrogen into an electric-arc reactor allows for the efficient production of a new family of stable endohedral fullerenes encapsulating trimetallic nitride clusters, Er
2
—SC
3
—N@C
80
(x=0-3). The trimetallic nitride template process generates milligram quantities of product containing 3-5% Sc
3
N@C
80
, allowing isolation of the material and determination of the crystal structure, optical and electronic properties. The Sc
3
N moiety is encapsulated in a highly symmetric, icosahedral C
80
cage, which is stabilized as a result of charge transfer between the nitride cluster and the fullerene cage. Their method provides access to a range of small-bandgap fullerene materials whose electronic properties can be tuned by encapsulating nitride clusters containing different metals and metal mixtures. Although Stevenson et al. have described a new type of endohedral metallofullerene that contains anywhere from 0-3 atoms, they fail to provide a specific use for these materials. Moreover, since the atoms contained within the fullerene cage are all the same, the versatility of the compounds is greatly restricted.
An object of the present invention is to provide a method for imaging and treating an area of a body which employs at least one trimetallic nitride template endohedral metallofullerene compound having at least one diagnostic atom and at least one treatment atom encapsulated within a fullerene cage such that the diagnostic atom is different from the treatment atom.
Another object of the present invention is to provide a method for imaging and treating an area of the body that is versatile and amenable to many different applications in a body.
SUMMARY OF THE INVENTION
The aforementioned objects were accomplished by the present invention which is directed toward a method for imaging and treating an area of a body. The method comprises the steps of providing at least one trimetallic nitride template endohedral metallofullerene compound. The metallofullerene compound has at least one diagnostic atom and at least one treatment atom encapsulated within a fullerene cage. The diagnostic atom is different from the treatment atom. The trimetallic nitride template endohedral metallofullerene compound is administered into a body and is traced to an area of the body. The treatment atom is then permitted to react in the area of the body. The novel feature of this invention is that it employs a mixed metal cluster encapsulated within the fullerene cage. Since at least two of the three metals are different from each other, it is possible to have both a diagnostic and a treatment atom contained within the same fullerene cage.
Additional objects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention will be obtained by means of instrumentalities in combinations particularly pointed out in the appended claims.
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Lon J. Wilson, “Medical Applications of Fullerenes and Metallofullerenes,”Interface, Winter 1999, p. 24-28, The Electrochemical Society.
S. Stevenson et al., “Small-Bandgap Endohedral Metallofullerenes in High Yield and Purity,”Nature, Sep. 2, 1999, p. 55-57, vol. 401.
S. Stevenson et al., “A Stable Non-Classical Metallofullerene Family,”Nature, Nov. 23, 2000, p. 427-428, vol. 408.
Chun-Ru Wang et al., “C66Fullerence Encaging A Scandium Dimer”,Nature, Nov. 23, 2000, p. 426, vol. 408.
Haruhito Kato et al., “Evaluation of Water-Soluble Metallofullerenes for MRI Contrast Agents,”Abstracts of the 20thFullerene General Symposium, Jan. 22-23, 2001, p. 38.
Kymbr L. S. Lawrence and Garyl J. Ehrhardt, “Fullerene Radiopharmaceuticals? High-Flux Neurton Irradiation Study of C60,” Electrochemical Society Proceedings, Date unknown, p. 66-71, vol. 95-10.
Dawson W. Cagle et al., “Synthesis, Characterization and Neutron Activation of Holmium Metallofullerenes,”Journal of American Chemical Society, 1996, p. 8043-8047, vol. 118.
Dawson W. Cagle et al., “In Vivo Studies of Fullerene-Based Materials Using Endohedral Metallofullerene Radiotracers,”Proceedings of the National Academy of Science, Apr. 1999, p. 5182-5187, vol. 96.
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Dorn Harry C.
Luo Shufang
Miller Michael B.
Murphy Kent A.
Stevenson Janice P.
Bryant Joy L.
Jones Dameron L.
Luna Innovations Inc.
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