312 results about "Isotopic labeling" patented technology

The invention relates to techniques for measuring and comparing relative molecular flux rates of different biological molecules by administering isotope-labeled water to one or more tissues or individuals and comparing the molecular flux rates of two or more biological molecules, including biological molecules in different chemical classes. The methods find use in several applications including diagnosing, prognosing, or monitoring a disease, disorder, or condition, the in vivo high-throughput screening of chemical entities and biological factors for therapeutic effects in various disease models, and the in vivo high-throughput screening of chemical entities and biological factors for toxic effects.

The present invention provides novel amino acid compounds useful in detecting and evaluating brain and body tumors. These compounds have the advantageous properties of rapid uptake and prolonged retention in tumors and can be labeled with halogen isotopes such as fluorine-18, iodine-123, iodine-124, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77, bromine-82, astatine-210, astatine-211, and other astatine isotopes. These compounds can also be labeled with technetium and rhenium isotopes using known chelation complexes. The compounds disclosed herein bind tumor tissues in vivo with high specificity and selectivity when administered to a subject. Preferred compounds show a target to non-target ratio of at least 2:1, are stable in vivo and substantially localized to target within 1 hour after administration. Preferred compounds include 1-amino-2-[¹⁸F]fluorocyclobutyl-1-carboxylic acid (2-[¹⁸F]FACBC) and 1-amino-2-[¹⁸F]fluoromethylcyclobutyl-1-carboxylic acid (2-[¹⁸F]FMACBC). The labeled amino acid compounds of the invention are useful as imaging agents in detecting and/or monitoring tumors in a subject by PET or SPECT.

A method for intracellular metabolic flux analysis comprising (a) culturing cells in a medium not containing any isotope-labeled substrate to a target phase of the metabolic flux analysis, (b) adding an isotope-labeled substrate to the medium, and continuing culture and collecting samples from the medium in time course, (c) measuring isotope distribution in an intracellular metabolite contained in the samples collected in time course, (d) performing a regression analysis for measured data and calculating an isotope distribution ratio in a steady state, and (e) analyzing a metabolic flux of the cultured cells by using the calculated isotope distribution ratio.

The invention enables high-throughput screening of compounds in living systems to detect unanticipated or unintended biological actions. The invention also allows for screening, detection, and confirmation of new indications for approved drugs. Screening and detection of toxic effects of compounds also can be achieved by using the methods of the invention. The methods comprise administering isotope-labeled substrates to a living system so that the label is incorporated into molecules in a manner that reveals flux rates through metabolic pathways thought to be involved in a disease. Comparisons between living systems exposed to compounds and living systems not so exposed reveals the effects of the compounds on the flux rates through the metabolic pathways. Combinations or mixtures of compounds can be systematically screened to detect unanticipated or unintended biological actions, including synergistic actions, in the same manner.

A method for analyzing an intracellular metabolic flux comprising determining the intracellular metabolic flux from analytical values of cells cultured in a medium containing an isotope-labeled substrate as a carbon source on the basis of an intracellular metabolic flux model constructed for the intracellular metabolic flux to be analyzed, wherein (a) influence of an exchange reaction between an intracellular metabolite and a cell component produced by integration of the intracellular metabolite is considered, (b) uptake of a compound in a medium into cells, which compound is identical to an intracellular metabolite and unlabeled with an isotope, is considered, or (c) carbon dioxide used in a fixation reaction is assumed as carbon dioxide produced in a production reaction.

The present invention provides methods and kits useful for determining rates of replication and destruction of an infectious agent within an infected host organism. In the methods of the invention, an isotopically-labeled precursor molecule is administered to an infected host, and is given sufficient time to pass into the host's metabolic pools into a biochemical component of the infectious agent. The isotopic content and/or pattern or the rate of change of the isotopic content and/or pattern of the biochemical component is then measured to determine the rate of replication (growth) of the infectious organism while in the host. Alternatively, isotopic decay of labeled molecular components of the infectious agent is measured over time after discontinuing administration of the isotopically labeled precursor molecule to determine the rate of destruction (death) of the infectious agent while in the host. Thus, using methods of the invention, in vivo sensitivity of infectious agents to drug agents may be determined, in order to optimize therapy of the infected host.

Optimized enzymatic conditions incorporate a single oxygen atom into digested peptides using a peptidase. The incorporation of a single oxygen atom is especially useful for proteolytic ¹⁸O labeling in comparative proteomics. The optimized proteolytic ¹⁸O labeling minimizes the generation of a mixture of isotopic isoforms of the peptides resulting from incorporation of either one or two ¹⁸O atoms. The outcome is accurate quantification of isotopically labeled peptides.

Provided herein are methods for measuring protein biosynthesis by using ²H₂O or radioactive ³H₂O and applicable uses thereof.

In one aspect, the present invention provides a method for labeling a terminal olefin, the method comprising a step of treating a terminal olefin substrate having the structure:

with a labeled ethylene reagent in the presence of a suitable catalyst under suitable olefin metathesis reaction conditions to form a labeled terminal olefin having the structure:

wherein R^A and R^B are independently hydrogen, or an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl or heteroaryl moiety, with the proviso that R^A and R^B are not each hydrogen, or R^A and R^B taken together with the carbon atom to which they are attached form an alicyclic or heterocyclic moiety; and * denotes the presence of an isotopic label on the terminal carbon atom.

The invention discloses a method used for determining plant total photosynthesis carbon assimilation capacity. According to the method, double-way isotope labeling and a double source isotope mixed module are adopted to determine using ratio of plant on added bicarbonate ions and using ratio of plant on bicarbonate ions come from atmospheric carbon dioxide dissolving; a photosynthesis device is adopted to determine photosynthesis assimilation capacity of plant on atmospheric carbon dioxide; and plant total photosynthesis carbon assimilation capacity is obtained finally. The method is used for measuring using capacity of plant on added bicarbonate ions, and measuring using capacity of plant on bicarbonate ions come from atmospheric carbon dioxide dissolving; and influences of old carbon on determination results are avoided; so that obtained plant total photosynthesis carbon assimilation capacity data is reliable, and result accuracy is high.

The present invention provides agents and methods for dual modality virtual colonoscopy that gives both anatomical and functional information using hybrid CT/PET scanning. In preferred embodiments, the present invention provides radiolabeled tumor-specific agents and methods for distinguishing benign polyps from malignant tumors. In further embodiments, the present invention provides compositions and methods useful for distinguishing morphological and functional subregions of a selected region of tissue based on relative levels of phospholipid metabolism. Preferred radiolabeled tumor-specific agents are phospholipid ether analogs labeled with a halogen radiosiotope. In certain preferred embodiments, the compositions including radiolabeled phospholipid ether analogs have therapeutic actions in addition to functionally identifying malignant tissue.

The present invention relates to a method for associating information with an article, an isotopic labeling composition to label an article with information using at least two different isotopes of an element, and an article labeled with the labeling composition. In the labeling composition, the isotopes of the labeling composition have an abundance ratio that is detectably different from the natural abundance ratio thereof. By detecting the abundance ratio(s) of the isotopes in the labeling composition, via laser ablation/magnetic spectroscopy, an NQR spectrometer, an NMR spectrometer, an IR spectrometer, or a microwave spectrometer, information about the article can be determined. The invention may be used to identify, authenticate or determine the source or origin of an article or to provide detailed information about an article.

Provided herein are method for measuring the rate of synthesis, breakdown, transport, or other kinetic parameters of a protein in a tissue of medical interest, without requiring physical sampling of the tissue, by a measurement of the protein in a body fluid. Methods may include selecting one or more target proteins in a tissue; administering an isotope-labeled molecule to a subject for a period of time sufficient for said isotope-labeled molecule to enter into and label the one or more target proteins to produce one or more isotope-labeled target proteins; collecting a volume of a body fluid, wherein the volume comprises one or more isotope-labeled target proteins that escaped or were released from the tissue; enriching or isolating the one or more isotope-labeled target proteins from the volume; performing a mass spectrometric measurement of the isotopic content, rate of incorporation, and/or pattern or rate of change in isotopic content and/or pattern of isotope labeling of the one or more enriched or isolated isotope-labeled target proteins; and calculating at least one kinetic parameter of the one or more enriched or isolated isotope-labeled target proteins, where the kinetic parameter of the one or more isotope-labeled target proteins from the volume of a body fluid reflects the corresponding kinetic parameter of the one or more target proteins in the tissue; and inferring the at least one kinetic parameter of the one or more target proteins in the tissue based on the corresponding at least one kinetic parameter of the one or more target proteins in the body fluid.