The vascular system includes arteries, veins, arterioles, venules, and capillaries. Examples of cardiovascular diseases include diseases of the heart, such as myocardial infarction, myocardial ischemia, angina pectoris, congestive heart failure, cardiomyopathy congenital or acquired , arrhythmia, or valvular heart disease. In particular embodiments, the subject is known or suspected to have myocardial ischemia.
The subject, for example, may be a patient who presents to a clinic with signs or symptoms suggestive of myocardial ischemia or myocardial infarction. Imaging of the heart of the subject to diagnose disease may involve administering to the subject a pharmaceutically effective amount of a metal ion labeled chelator-targeting ligand conjugate synthesized using any of the methods set forth herein. Imaging can be performed using any imaging modality known to those of ordinary skill in the art.
In particular embodiments, the metal ion-labeled radionuclide-targeting ligand conjugate is 99m-Tc-EC-glucosamine. Glucosamine is not actively taken up by viable myocardial tissue but rather is target specific for regions of ischemia.
Severity of ischemia can be visually assessed or graded depending on magnitude of the signal that is measured using any method known to those of ordinary skill in the art. In some embodiments, imaging using any of the conjugates set forth herein is performed before, during, or after imaging of the heart using a second imaging agent. For example, the second imaging agent may be thallium imaged by scintigraphy to would define the region of normal myocardial perfusion non-ischemic tissue.
Myocardial perfusion SPECT MPS consist of a combination of a stress modality exercise or pharmacologic with rest and stress administration and imaging of radiopharmaceuticals.
Thallium has excellent physiologic properties for myocardial perfusion imaging. Being highly extracted during the first pass through the coronary circulation, a linear relationship between blood flow to viable myocardium and thallium uptake has been shown during exercise; however, at very high levels of flow, a "roll-off' in uptake occurs. As an unbound potassium analogue, thallium redistributes over time.
Its initial distribution is proportional to regional myocardial perfusion and at equilibrium, the distribution of thallium is proportional to the regional potassium pool, reflecting viable myocardium. The mechanisms of thallium redistribution are differential washout rates between hypoperfused but viable myocardium and normal zones and wash-in to initially hypoperfused zones. The washout rate of thallium is the concentration gradient between the myocardial cell and the blood. There is slower blood clearance of thallium following resting or low-level exercise injection.
Diffuse slow washout rates, mimicking diffuse ischemia, may be observed in normal patients who do not achieve adequate levels of stress. Hyperinsulinemic states slow redistribution, leading to an underestimation of viable myocardium; thus fasting is recommended prior to and for 4 hrs following thallium injection. This is why if EC-G is used as an viable agent in combination with thallium it will target the precise area of interest which would be the Ischemic but viable area see Angello et at.
Imaging using any of the metal ion-labeled chelator-targeting ligand conjugates of the present invention may also be performed in conjunction with other diagnostic methods, such as measurement of cardiac isozymes, or cardiac catheterization. The imaging may be performed at various intervals following onset of symptoms, or can be performed to assess for changes in myocardial perfusion over time.
Further embodiments pertain to a method of imaging a site within a subject comprising a administering to the subject a diagnostically effective amount of a metal ion labeled-chelator-targeting ligand conjugate, wherein the metal ion-labeled chelator-targeting ligand conjugate is synthesized by any of the methods set forth herein; and b detecting a signal from the metal ion labeled-chelator-targeting ligand conjugate that is localized at the site.
In specific embodiments, the metal ion labeled-chelator-targeting ligand conjugate comprises ethylenedicysteine. The signal can be detected by any method known to those of ordinary skill in the art. The subject can be any subject, such as a mammal or avian species. In particular embodiments, the mammal is a human. The site to be imaged can be any site in a subject, and may include, for example, a tumor, heart, lung, esophagus, muscle, intestine, breast, prostate, stomach, bladder, liver, spleen, pancreas, kidney, a tumor, duodenum, jejunum, ileum, cecum, colon, rectum, salivary gland, gall bladder, urinary bladder, trachea, larynx, pharynx, aorta, artery, vein, thymus, lymph node, bone, pituitary gland, thyroid gland, parathyroid gland, adrenal gland, brain, cerebrum, cerebellum, medulla, pons, spinal cord, nerve, skeletal muscle, smooth muscle, bone, testes, epidiymides, prostate, seminal vesicles, penis, ovary, uterus, mammary gland, vagina, skin, eyes, or optic nerve.
In particular embodiments, the site to be imaged is a tumor. In further particular embodiments, the site to be imaged is the heart. In some embodiments, the method of imaging further comprises performing one or more additional diagnostic or imaging procedures to evaluated the subject for a disease.
In further embodiments, the method of imaging is further defined as a method of performing dual imaging and therapy. In certain embodiments, the disease to be treated is a cardiovascular disease.
Non-limiting examples of such diseases include myocardial infarction, congestive heart failure, cardiomyopathy, valvular heart disease, an arrhythia, congenital heart disease, and angina pectoris.
The present invention also generally pertains to methods for imaging the brain or spinal cord neuroendocrine system of a subject, comprising administering to a subject one or more of the conjugates of the present invention.
In some embodiments, for example, the chelate is conjugated to a targeting ligand that is capable of crossing the blood-brain barrier of a subject. A non-limiting example of such a targeting ligand is an amino acid, such as tyrosine or an analog of tyrosine such as alpha-methyl tyrosine.
Other examples include somatostatin, octreotide, and tryptophan. The present invention also generally pertains methods of treating a subject with a disorder of the central nervous system of a subject. The disorder of the central nervous system may be, for example, a neurodegenerative disease such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer disease, or a neuroendocrine tumor.
Examples of neuroendocrine tumors include primary and metastatic brain tumors. Accordingly, intense drug discovery programs have led to the synthesis of new sulfonamide derivatives 7 — The direct synthesis of N-arylsulfonamides via the formation of N-S band is the most general approach 7 — Although these methods are efficient, they have two major drawbacks which limit their usefulness.
Firstly, they use aromatic amines which are carcinogens 11 and secondly, they lead to impure products. Other important methods for the synthesis of N-arylsulfonamide derivatives is the reaction of sulfonamides as nucleophiles with some organic compounds such as halides 12 — 15 , alcohols 16 — 21 , aryl esters 22 — 24 and arylboronicacids 25 — In another efficient strategy, N-arylsulfonamides were synthesized by the reaction of sulfonyl azides or hydrazides with benzoic acids 29 or arylboronic acids The main problem of these methods is the use of metal ions such as iridium, copper and palladium which pollute the environment.
In this context, we synthesized some new sulfonamide derivatives, via electrochemical oxidation of anilines 31 — 33 , urazoles 34 , 35 , nitroso aromatic compounds 36 — 38 and 1,2-dihydropyridazine-3,6-dione 39 in the presence of sulfone derivatives. The synergetic action of sulfonamides with trimethoprim has brought about an enormous resurgence of sulfonamide usage in many areas over the past decade. BertheletteA mild, efficient method for the synthesis of aromatic and aliphatic sulfonamides.
Tetrahedron Lett. Kevin Lopez 5 days ago Imidazolesulfonyl azide hydrogen sulfate is presented as an efficient reagent for the synthesis of sulfonyl azides from primary sulfonamides.
The described method is experimentally simple and high-yielding and does not require the addition of Cu salts.
Mark Scott 16 days ago A series of novel sulfanilamide-derived 1,2,3-triazole compounds were synthesized in excellent yields via 1,3-dipolar cycloaddition and confirmed by MS, IR and NMR spectra as well as elemental analyses. All the compounds were screened in vitro for their antibacterial and antifungal activities. Preliminary results indicated that some target compounds exhibited promising antibacterial potency. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of Donald Walker 19 days ago The present invention concerns bio-nano power cells and methods of their manufacture and use.
More particularly, the present invention relates to the preparation of bio-nano power cells that are biocompatible and capable of producing flash, intermittent, or continuous power by electrolyzing compounds in biological systems. Steven Thomas 27 days ago USA1 - Antiviral compounds - Google Patents Anthony Adams 23 days ago Microbes are unique creatures that adapt to varying lifestyles and environment resistance in extreme or adverse conditions.
The genetic architecture of microbe may bear a significant signature not only in the sequences position, but also in the lifestyle to which it is adapted. It becomes a challenge for the society to find new chemical entities which can treat microbial infections.The subject can be any subject, such as a mammal or animal models used to assess the presence of cardiovascular disease. Mark Turner 20 days ago Acidic sulfonyl hydrazone derivatives have analgesic and anti In further embodiments, the targeting ligand is a disease receptor targeting ligand. Introduction Sulfonamides are an important class of organic compounds with antibacterial activity 1 toward gut infections, Pneumocystis jirovecii pneumonia, urinary tract infections, mucous membrane, toxoplasma encephalitis, Kaposi sarcoma herpes virus infection and isospora infections in HIV infection 2 , 3.
In still further embodiments, the metal ion labeled chelator-targeting ligand conjugate is Re-EC-glucosamine. Examples of COX-2 inhibitors include celecoxib, rofecoxib, and etoricoxib. Metal catalysts, unsafe solvents, tedious workup and harsh reaction conditions are disadventages associated with these methods. In particular embodiments, the mammal is a human.
Other exemplary anti-cancer ligands include, for example, epipodophyllotoxin, vincristine, docetaxel, paclitaxel, daunomycin, doxorubicin, mitoxantrone, topotecan, bleomycin, gemcitabine, fludarabine and 5 -FUDR. More examples are set forth below. For example, the second imaging agent may be thallium imaged by scintigraphy to would define the region of normal myocardial perfusion non-ischemic tissue. In some embodiments, the kit includes one or more vials containing a composition comprising disodium hydrogen phosphate dehydrate, mannitol, ascorbic acid, sodium edentate, stannous chloride dehydrate, tartaric acid, or potassium dihydrogen-phosphate, and a pharmaceutically acceptable carrier.
The imaging may be performed at various intervals following onset of symptoms, or can be performed to assess for changes in myocardial perfusion over time. Heterocycles containing pyrimidine moiety are of great interest because they constitute an important class of natural and nonnatural products, many of which exhibit useful biological activities In preferred embodiments, the subject is a human with known or suspected cardiovascular disease. In some embodiments, the targeting ligand is a gene expression marker. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of
The present invention also relates to a method for diagnosing a cardiovascular disease in a subject, comprising imaging a site in the subject by detecting a signal from the metal ion labeled-chelator-targeting ligand conjugate that is localized at the site. Mark Wilson 29 days ago tetra tosylate tmp: Topics by Science. In this context, we recently reported the synthesis of some new sulfonamide derivatives, using simple nitroarenes and sodium arylsulfinates as starting materials, under green conditions In another efficient strategy, N-arylsulfonamides were synthesized by the reaction of sulfonyl azides or hydrazides with benzoic acids 29 or arylboronic acids In specific embodiments, the metal ion labeled-chelator-targeting ligand conjugate comprises ethylenedicysteine.
Metal catalysts, unsafe solvents, tedious workup and harsh reaction conditions are disadventages associated with these methods. The targeting ligand may also be glutamate pentapeptide. For example, the cancer may be breast cancer, lung cancer, prostate cancer, ovarian cancer, brain cancer, liver cancer, cervical cancer, colon cancer, renal cancer, skin cancer, head and neck cancer, bone cancer, a esophageal cancer, bladder cancer, uterine cancer, lymphatic cancer, stomach cancer, pancreatic cancer, testicular cancer, lymphoma, or leukemia.
In some embodiments, the targeting ligand is an antimetabolite. In particular embodiments, the agent that mimics glucose is glucosamine.
In other examples, the metal ion is a radionuclide. The synergetic action of sulfonamides with trimethoprim has brought about an enormous resurgence of sulfonamide usage in many areas over the past decade. In certain embodiments, the disease to be treated is a cardiovascular disease.
The targeting ligand may also be glutamate pentapeptide. In some embodiments, the disorder of the central nervous system is an inflammatory disease. Pyrimidine: General Introduction. Certain embodiments pertain to methods of performing dual imaging and therapy in a subject. In a particular embodiments, the cold metal ion is Re Non-limiting examples of peptides contempated as targeting ligands include neuropeptide Y, calcitonin gene-related peptide, substance P, and vasoactive intestinal peptide.