Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing
Reexamination Certificate
2001-08-13
2002-04-30
Jones, Dameron L. (Department: 1619)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
C424S001110, C424S001650, C534S014000
Reexamination Certificate
active
06379650
ABSTRACT:
BACKGROUND OF THE INVENTION
1. The background of the invention pertains to the field of medical radioimaging; specifically, the radioimaging of amyloid proteins in biological organisms such as human patients using a Technecium isotope (
99m
Tc) for radiolabeling congo red. The present invention discloses multiple
99m
Tc-labeled congo red complexes and their precursors utilizing various diamide dithiolate ligand systems and disclosing convenient methods for making these products, thereby providing a cost effective and practical means for enhancing the radioimaging of amyloid by standard nuclear medicine techniques.
2. Description of the Prior Art
Amyloidosis is a term applied to a group of disorders (e.g. chronic inflammatory diseases, infections, and neoplasms) associated with the deposition of insoluble fibrillar proteins within various organs of the body, which results in significant morbidity and mortality. There are other diseases such as Alzheimer's disease that are associated with nonsystemic, organ specific amyloid deposits. Before radioimaging, the only practical means for diagnosing amyloid in the tissues was by tissue biopsy.
In 1922, it was demonstrated that intravenous congo red cleared faster from the blood of patients having significant systemic amyloidosis. In the 1960's, radiolabeled congo red was used to photometrically determine plasma clearance and in 1962, scientists demonstrated localization of amyloid deposits in the livers and spleens of patients with systemic amyloidosis using nuclear medicine radioimaging techniques and I
131
-radiolabeled congo red. However, I
131
is a radioisotope having a significantly long half-life. Recently, Han et al. disclosed a
99m
Tc-radiolabeled congo red complex utilizing a bipyridyl analogue (
J. Am. Chem. Soc
., 118:4506-4507, 1996). Technicium-99m radioisotope has the advantage of a short half-life; however, the bipyridyl analogue of congo red disclosed by Han et al. is apparantly difficult to produce. The present application discloses several
99m
Tc-radiolabeled congo red complexes and their precursors that utilize one of multiple diamide dithiolate (N
2
S
2
) ligand systems conjugated to the Congo red molecule. These
99m
Tc-radiolabeled congo red complexes and their precursors utilize diamide dithiolate (N
2
S
2
) ligand systems that rely upon well defined chemistries and are practical to produce for onsite use. Some of the precursors are suitable for storage as stable salts, and can be complexed with
99m
Tc when needed.
SUMMARY OF THE INVENTION
It is a primary object of the invention to overcome the shortcomings of the prior art radiolabeled congo red complexes by providing a
99m
Tc-radiolabeled congo red complex that utilizes a diamide dithiolate (N
2
S
2
) ligand system.
It is a primary object of the invention to provide a
99m
Tc-radiolabeled congo red complex utilizing a diamide dithiolate (N
2
S
2
) ligand system that is practical to produce.
It is a primary object of the invention to provide a
99m
Tc-radiolabeled congo red complex utilizing a diamide dithiolate (N
2
S
2
) ligand system that is practical to use as a radioimaging agent in warm blooded animals and human patients.
It is a primary object of the invention to provide a
99m
Tc-radiolabeled Congo red complex utilizing a diamide dithiolate (N
2
S?) ligand system that is suitable for intravenous or intrathecal administration to a warm blooded animal or human patient.
It is a primary object of the invention to provide a congo red complex precursor utilizing a diamide dithiolate (N
2
S
2
) ligand system that forms a stable salt for long term storage and that can be subsequently complexed with
99m
Tc to form a
99m
Tc-radiolabeled Congo red complex utilizing a diamide dithiolate (N
2
S
2
) ligand system.
REFERENCES:
patent: 4746505 (1988-05-01), Jones et al.
patent: 5039511 (1991-08-01), Quay et al.
patent: 5080883 (1992-01-01), Lyle et al.
patent: 5095111 (1992-03-01), Lever et al.
patent: 6168776 (2001-01-01), Klunk et al.
Han, H., Cheon-Gyn, C., and Landsbury, P.T.: Technetium Complexes for the Quantification of Brain Amyloid, J.Am.Chem.Soc. 118:4506-7, 1996.
Fritzberg et al.: “Specific and Stable Labeling of Antibodies with Technecium—99m with a Diamide Dithiolate Chelating Agent.” Proc. Natl. Acad.Sci. 85:4025-4029, 1988.
Lever et al.: Synthesis of a Novel BiFunctional Chelate Designed for Labeling Proteins with Technetium—99m. Tetra. Lett. 29:3219-3222, 1988.
Lever et al.: “Pulmonary Accumulation of Neutral Diamine Dithiol Complexes of Technetium—99m.” J. Pharm. Sci. 83:802-809, 1994.
Baidoo et. al. BiFunctional Chelator for Facile Preparation of Neutral Technetium Complexes. Bioconjugate Chem. 5:114-118, 1994.
Ashton Wesley Scott
Jones Dameron L.
LandOfFree
Technetium 99m-N2S2-congo red complexes utilizing diamide... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Technetium 99m-N2S2-congo red complexes utilizing diamide..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Technetium 99m-N2S2-congo red complexes utilizing diamide... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2842152