Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Reexamination Certificate
1998-10-07
2001-06-12
Jones, Dameron L. (Department: 1619)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
C424S001110, C424S001650, C424S009300, C424S009100, C534S014000
Reexamination Certificate
active
06245316
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to novel compositions and methods for enhancing delivery of radioimaging and radioprotective agents.
BACKGROUND OF THE INVENTION
A radioimaging agent is administered for the purpose of visualizing various body tissues through the radiative properties of the agent, or the agent's interactions with high energy radiation. Computed axial tomography (CAT) and positron emission tomography (PET) are representative examples of radioimaging techniques currently in use for visualizing various physiological structures. Of particular interest is the imaging of in vivo tumors and the effects various therapeutics have on such a tumor. A radioimaging agent typically carries a radioactive tag or label that must reach a given organ that is being studied and must undergo a reaction or uptake that provides information related to the organ's condition or the presence of a tumor. For a radioimaging agent to be effective in visualizing tumors, malignant cells must differentially react with or uptake, an agent. Simple sugars and carbohydrates are major energy sources of cell metabolism and therefore represent a chemical structure well suited for modification into a radioimaging agent.
Polysaccharide based radioimaging and radioprotective agents are characterized by slow cellular uptake, owing to the size and transport mechanism of such large molecules. For example, U.S. Pat. No. 5,554,386 details the endocytosis of polysaccharide therapeutics. In contrast to polysaccharides, monosaccharides and disaccharides in general, and glucose in particular, cross cellular membranes by active transport and frequently in conjunction with ion transport associated with the membrane potential. Because of the high diffusion rates and active transport of mono- and disaccharides, these molecules are more readily internalized within cells.
There are a number of radioisotopes suitable for use as radioimaging agents. The choice of radioisotope depends on factors including: isotope lifetime, modes of decay, decay energy, particle emission energies and neutron capture cross-sections. Radioisotopes are selected for particular radioimaging tasks based on the compatibility of the radioisotope properties with the imaging detector system, storage requirements and toxicity. Since the toxicity typically decreases and cellular uptake rates increase by bonding the radioisotope to a suitable carrier, one must further balance the synthetic chemistry necessary to bond a selected radioisotope to a carrier molecule against the imaging properties of the selected radioisotope. Previous efforts have involved bonding radioisotopes of fluorine, carbon and iodine to glucose or glucose-like molecules; for example, see U.S. Pat. No. 4,789,542. Still other efforts have involved coating an inorganic core with carbohydrate molecules to facilitate cellular delivery; for example, see U.S. Pat. No. 5,582,172.
There is also an important need for radioprotective agents. A radioprotective agent functions to protect critical body tissues against low to moderate doses of ionizing radiation and the in situ generated free radicals associated with biological tissues being exposed to such radiation. Radioprotective agents are beneficially administered to patients receiving radioisotope and radiation treatments, as well as to protect individuals entering radiation contaminated environments. Such a radioprotective agent serves antimutagenic and anticarcinogenic roles within tissues containing such an agent. Delivery of radioprotective agents has previously proven to be a limiting factor in their use; for example, see U.S. Pat. No. 5,167,947. To this end, the mono- and disaccharides of the instant invention serve as effective carriers for radioprotective moieties.
BRIEF DESCRIPTION OF THE INVENTION
Disclosed herein is a pharmaceutical composition for enhancing the delivery of a radioimaging or radioprotective agent in vivo. The agent comprises a carbohydrate which is capable of binding to, or penetrating a target cell. The carbohydrate has attached thereto either a radioisotope or a free radical scavenger moiety, and the composition further includes a carrier suitable for delivery of the carbohydrate to the target cell. In some embodiments, the radioactive isotope is an isotope of technetium, carbon or gadolinium. In those instances where the composition includes a radical scavenger, the radical scavenger may comprise an aminoalkylaminoethyl phosphorothiolate.
The invention also includes a method of imaging a cancerous tumor which comprises contacting the tumor with a radiolabeled carbohydrate, allowing sufficient time for said carbohydrate to enter the tumor and recording a radioimage of the tumor using radioimaging techniques. In one preferred method, the carbohydrate comprises D-glucose. The invention further includes a method for delivering a bioactive radioprotectant to an animal which comprises binding the radioprotectant to a carbohydrate and administering it to the animal. One preferred carbohydrate comprises D-glucose and one preferred radioprotectant that comprises ethiofos or a metabolite thereof.
The invention further includes a radioimaging material comprising a glucoside of a radioisotope of gadolinium, and in one embodiment, the material comprises a radioisotope of gadolinium bonded to three molecules of glucose.
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Gifford, Krass, Groh Sprinkle, Anderson & Citkowski, P.C.
Jones Dameron L.
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