Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Reexamination Certificate
2000-03-03
2003-08-05
Jones, Dameron L. (Department: 1616)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
C424S001110, C424S009100
Reexamination Certificate
active
06602488
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to the radiopharmaceutical labeling of diseased or malfunctioning candidate cells for subsequent treatment with a medicinal compound, the identification in situ of the candidate cells using a probe sensitive to the presence of the radiopharmaceutical label and then treatment of the identified cell. Addressed are improved instruments with enhanced operability, controllability, diagnostic capability and treatment capability. For example, the described devices can be used in an MRI environment, can provide a visual image as well as a radiation image, allow 3D imaging, and allow delivery of treatment compounds to the cell while the probe is at the site of the labeled cells. In one embodiment, the invention relates to in situ gene therapy using a beta or gamma probe to locate labeled cells, also referred to as candidate cells, and the delivery of corrective or therapeutic genes to the candidate cells identified by the probe while the probe is positioned adjacent to the labeled and located cells.
DESCRIPTION OF THE PRIOR ART
Most of the basic elements of biological materials have radiation emitting isotopes (e.g., C-11, N-13, O-15, F-18, I-124). For example, these compounds can be labeled with isotopes which emit positron, beta or gamma rays. More than 500 biochemicals have been labeled with these isotopes (e.g., amino acids, fatty acids, sugars antibodies, drugs, neuroreceptor ligands, nucleoside analogues, etc).
Recently, several chemical compounds have been labeled with various positron emitting tracer isotopes for the imaging of gene expression. For example I-124 labeled FIAU a 2′-fluoro-substituted nucleotide analogue, and PET studies performed on rats (Tjuvajev et al. Cancer Res 55, 6126-6132 (1995); Tjuvajev et al. Cancer Res 56, 4087-4095 (1996); Tjuvajev et al. Cancer Res. (1999) in Press) [8-F
18
]-fluoroganciclovir has been used for PET studies of gene transduction in mice (Gambhir et al. J. Nucl. Med. (in Press) (1998); Haberkorn U et al. J Nucl. Med. 38: 1048-1054 (1997)). The goal of these procedures was to introduce radiolabeled tracers after gene therapy to determine if the gene therapy was successful. The presently described invention is fundamentally different because the below described invention entails radiolabeling of cells suitable for gene therapy and providing a gene therapy composition directly to labeled cells while targeted by the probe.
In attempts to locate cancerous cells numerous labeling techniques have been developed to identify the site of those cancerous cells. It was recognized many years ago that fibrin, while not a tumor specific antigen, was known to be more prevalent in the vicinity of tumors due to the inflammatory process accompanying the cell proliferation. Therefore radiolabeled immunoglobulin was used for tumor localization (Day, E. O.; Planisek, J. A.; Pressman D.; “Localization of Radioiodinated Rat Fibrinogen in Transplanted Rat Tumors”,
J. Natl. Cancer Inst
. 23: 799-812, 1959. Sparr, J. L.; Bale, W. F.; Marrock, D. D.; Dewey, W. O.; McCardle, R. J.; Harper, P. V.; “Labeled Antibodies to Human Fibrinogen. Diagnostic Studies and Therapeutic Trails”,
Cancer
, 20: 865-870, 1967.) In all these works the goal was to use radiolabled tracers after gene therapy to determine if the gene therapy was successful. The new method described in this patent application is fundamentally different because radio labeled tracers are used to locate the cells that are suitable candidates for gene therapy before the therapy is applied.
More specific labeling was accomplished by Goldbenberg, et al. by the use of I
131
-labelled heterologous (goat) antibodies to human carcinoembryonic antigen (CEA). (Goldenberg, D. M.: “Oncofetal and other Tumor-associated Antigens of the Human Digestive System”,
Curr. Top. Pathol
. 63: 289-342, 1976. Goldenberg, D. M.; Deland, F.; Kim, E. E.: “Human Chorionic Gonadotrophin Radioantibodies in the Radio immunodetection of Cancer and the Disclosure of Occult Metastases”
Proc. Nat'l. Acad. Sci
. 78: 7754-7758, 1981.; Goldenberg, D. M.; Deland, F.; Kim, E. E., et al.: “Use of Radio labeled Antibodies to Carcinoembryonic Antigen for the Detection and Localization of Diverse Cancers by External Photoscanning”,
N. Engl. J. Med
. 298: 1384-1388, 1978.; Goldenberg, D. M.; Preston, D. F.; Primus, F. J.; Hansen, H. J.: “Photoscan Localization of GW-39 Tumors in Hamsters Using Radiolabeled Anticarcinoembryonic Antigen Immunoglobulin”
J. Cancer Res
. 34: 1-9, 1974.; Goldenberg, D. M.; Sharkey, R. M.; Primus, F. J.: “Carcinoembryonic Antigen in Histopathology: Immunoperoxidase Staining of Conventional Tissue Sections”,
J. Natl. Cancer Inst
. 57: 11-22, 1976.) CEA is a tumor-associated antigen of gastrointestinal cancer, particularly colon and pancreatic cancer, first described by Gold. (Gold, P., Freedman, S. O.: “Demonstration of Tumor Specific Antigen in Human Colonic Carcinomata by Immunologic Tolerance and Absorption Techniques”,
J. Exp. Med
. 121: 439-462, 1965.) Other labeled antibodies usable for tagging tumor cells include monoclonal antibody 17-1A and its F(ab′)
2
fragment (Wistar Institute, Philadelphia, Pa.), monoclonal antibody 19-9 and its F(ab′)
2
fragment (Centocor, Inc., Philadelphia, Pa.), monoclonal antibody B72.3 (Dr. Jeffrey Schlom, National Cancer Institute) and CC49 and CC83, both second generation B72.3 antibodies. These are identified as examples of suitable materials and are not meant to limit the scope of compounds usable to label cells. Many other compounds, such as single chained antibodies (SCAs) disclosed in U.S. Pat. No. 4,946,778, capable of labeling specific cells, are identified in the literature and are constantly being discovered and/or developed. Labeling nucleotides detectable by a gamma probe include technetium Tc
99,
, iodine I
123,
, I
125
, and I
131
, indium In
111
, selenium Se
75
, and cobalt Co
57
. These and other radioisotopes can be detected by beta or gamma probes.
Martin et al., U.S. Pat. No. 4,782,840, incorporated herein by reference, describes a procedure which requires the administration of I
125
labeled antibody or antibody fragments to a patient to label cancerous tissue. Some time after administration (2 to 21 days) the suspected site is accessed surgically and, using a hand-held gamma probe, the labeled tissue is located and surgically removed.
Applicant is a co-inventor on U.S. Pat. Nos. 5,008,546, 5,325,855 and 5,338,937, which describe and claim variations to prior know intraoperative radiation probes. Others describe the use of gamma probes as a biopsy probe for locating, localizing or mapping tagged tissue located throughout the body and particularly near the liver, kidney, or blood vessels or to localize lymph nodes (U.S. Pat. Nos. 4,959,547, 5,170,055 and 5,036,201 to Carroll et al; U.S. Pat. No. 5,383,456 to Arnold et al.). Leone et al, U.S. Pat. No. 5,811,814 describes a catheter, including fiber optics and a scintillation crystal, suitable for locating concentrations of alpha, beta, gamma or X-ray labeled compounds introduced into the arteries and veins.
The use of radiation detection probes placed through scopes to locate radionuclide labeled tissue has been described in the literature for many years. Both Barber et al and Woolfenden et al. described the insertion of a gamma ray detection probe through an open channel in a broncoscope. (Barber, H. B., Woolfenden, J. M., Donahue, D. J., Nevin, W. S., “Small Radiation Detectors for Bronchoscopic Tumor Localization”,
IEEE Transactions on Nuclear Science
, NS-27, No. 1 Febuary 1980; Woolfenden, J. M., Nevin, W. S., Barber, H. B., Donahue, D. J., “Lung Cancer Detection Using a Miniature Sodium Iodide Detector and Cobalt-57 Bleomycin”,
Chest
, 85, 1, January 1984). Goldenberg, U.S. Pat. No. 4, 932,412, issued Jun. 12, 1990 claimed the same technique, namely the use of a radiation detection probe placed through an endoscope to locate radionuclide labeled tissue.
U.S. Pat. No. 5,846,513 to Carroll et al. describes a probe for percuta
Intramedical Imaging, LLC
Jones Dameron L.
Koppel, Jacobs Patrick & Heybl
Ram Michael J.
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