46 results about "Radioligand" patented technology

One embodiment of the invention is a composition that comprises a radioactive [18F], [123I], [125I], or [131I]—N-radiohaloaryl-alkylcarboxamide molecule. The composition binds to the transient receptor potential-M8 (TRP-M8) receptor of cells. The TRP-M8 receptor is selectively expressed in sensory neurons and in malignant tissues such as prostate cancer cells. The [18F], [123I], [125I], or [131I]—N-radiohaloaryl-alkylcarboxamide ligand may be used for radioreceptor binding studies, for diagnostic studies, and for radiotherapy of cancerous tissues. Affinity of the [125I] or [131I]—N-radiohaloaryl-alkylcarboxamide ligand for the TRP-M8 receptor confers selectivity and specificity in delivering lethal radiation to the diseased cells.

The present disclosure provides a method for preparing a radioactive ligand or radioactive substrate having affinity for a target biomacromolecule, the method comprising: (a) reacting a first compound comprising a first functional group capable of participating in a click chemistry reaction, with a radioactive reagent under conditions sufficient to displace the leaving group with a radioactive component of the radioactive reagent to form a first radioactive compound; (b) providing a second compound comprising a second complementary functional group capable of participating in a click chemistry reaction with the first functional group; (c) reacting the first functional group of the first radioactive compound with the complementary functional group of the second compound via a click chemistry reaction to form the radioactive ligand or substrate; and (d) isolating the radioactive ligand or substrate.

This invention relates to a novel method of screening for inhibitors of beta-amyloid production, and thereby identifying such inhibitors as therapeutics for neurological and other disorders involving APP processing and beta-amyloid production. This invention also relates to identifying macromolecules involved in APP processing and beta-amyloid production. Furthermore, inhibitors identified by the screening method of the present invention are useful in the treatment of neurological disorders, such as Alzheimer's disease, which involve elevated levels of Aβ peptides.

Analogs of SRIF which are selective for SSTR1 in contrast to the other cloned SRIF receptors. These analogs are useful in determining the tissue and cellular expression of the receptor SSTR1 and its biological role in the endocrine, exocrine and nervous system, as well as in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,5[D-Trp8, IAmp9, Tyr11]-SRIF and counterparts incorporating Cbm at the N-terminus, as well as radioiodinated versions thereof, inhibit the binding of a universal SRIF radioligand to the cloned human receptor SSTR1, but they do not bind with significant affinity to human SSTR2, SSTR3, SSTR4 or SSTR5. By incorporating an iodinated tyrosine in position-2 or in position-11 in these SSTR1-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. The N-terminus accommodates bulky moieties without loss of selectivity, and a carbamoyl moiety or a conjugating agent that will accept a radioactive nuclide or will link to a cytotoxin may be present at the N-terminus.

The invention provides a C-end phenylalanine p-amino modified endomorphine-1 analog. The N end of endomorphine-1 is modified by using guanidyl, Pro-Typ at the 2nd and 3rd positions of the endomorphine-1 is substituted by D-Ala-Gly, the benzene ring para-position at the 4th position is modified by using amino, and the novel analog [GAGPNH2]-EM-1 of the endomorphine-1 is synthesized by a liquid phase synthesis method. A series of physiological and pharmacological activity identification is performed on the analog through radioligand receptor binding experiment, in vitro enzymolysis stability experiment and warm bath drift analgesia experiment, and the results show that the analog has high affinity, high enzymolysis stability, high blood-brain barrier permeating capability and low side effect compared with parents of the analog. Therefore, the analog which is used as an active substance and used for preparing clinical analgesia medicaments has a good application prospect.

The invention discloses a non-natural amino acid modified endomorphin-1 analogue. A synthesis method comprises the following step: replacing amino acid phenylalanine at a fourth site from a terminal N to a terminal C of parent endomorphin-1 by respectively using 2-thienyl substituted alpha-alkenyl-beta-amino acid and 3-thienyl substituted alpha-alkenyl-beta-amino acid. The affinity and enzymatic hydrolysis stability of a mu opioid receptor of the non-natural amino acid modified endomorphin-1 analogue can be effectively improved, and thus the in-vivo analgesic effect of the non-natural amino acid modified endomorphin-1 analogue can be further improved and prolonged; and the non-natural amino acid modified endomorphin-1 analogue is subjected to pharmacological activity identification by virtue of radioligand receptor binding experiments, in-vitro organ biological assays and in-vitro enzymatic hydrolysis stability and warm bath tail-flick analgesic experiments, and results show that compared with parent endomorphin-1, the synthesized non-natural amino acid modified endomorphin-1 analogue disclosed by the invention has higher affinity, higher enzymatic hydrolysis stability and higher analgesic activity, and has potential application values of being taken as clinical polypeptide analgesic medicines.

Described herein are Tz / TCO-based pretargeting strategies using an Al[18F]-NOTA-labeled tetrazine radioligand. This imaging strategy enables delineation of cancer at earlier time points compared to other imaging strategies and further decreases the radiation dose to healthy tissues compared to directly labeled antibodies. Al-based 18F imaging of small molecules, such as tetrazine, has not been previously achieved due to the decomposition of tetrazine during radiofluorination. Radiofluorination is advantageous over other radiolabeling methods because, in addition to having a shorter half-life, 18F is more readily available to produce and therefore integrated into hospital workflows.

The invention relates to aromatase inhibitory activity high-throughput screening realized by means of a homogeneous time-resolved fluorescence technique. By detecting the fluorescence intensity ratio (665nm / 610nm) of an excitation light irradiated reaction system and performing formula conversion, the inhibitory activity of a to-be-detected sample on aromatase can be determined. By means of high-throughput screening new model, the harm of a radioligand binding principle-based experimental method to laboratory personnel and environment can be avoided. And the high-throughput screening model provided in the invention has the advantages of high efficiency, rapidity, accuracy, and inexpensiveness.

A method for positron emission tomography (PET) imaging of LRRK2 in tissue of a subject, the method comprising: administering a compound of formula I, formula II or formula III, or a pharmaceutically acceptable salt thereof to the subject, wherein the compound includes at least one C11 or F18 label thereon; allowing the compound to penetrate into the tissue of the subject; and collecting a PET image of the CNS or brain tissue of the subject.

The present invention relates to methods for determining whether a mammal has a disease, such as diabetes, using PET data analysis techniques. These methods include administering to a mammal a PET-compatible tracer, such as a radioligand specific for a vesicular monoamine transporter 2 (VMAT2) receptor, and measuring total functional β-cell capacity (volume) of the mammal's pancreas using PET data analysis techniques. Methods for tracking the efficacy of a treatment for diabetes, for evaluating the regeneration of β-cells in a pancreas, and for monitoring a patient with a transplanted pancreas are also provided.

The invention features a novel precursor provided for radioisotope labeling with ligands for specific binding of prostate-specific membrane antigen (PSMA) for prostate cancer diagnosis and treatment, and the pharmacophore of a PSMA inhibitor composed of three molecules of glutamic acid, urea and lysine is provided with three variable linkers based on pharmacological activity of the PSMA inhibitor for labeling with radioactive nucleus Ga-67, Ga-68, In-111, Lu-177, Cu-64, or Y-90 through a chelating agent for imaging analysis of human tumor models of prostate cancer and serving as a PSMA-targeted radioligand therapy for prostate cancer diseases.

One embodiment of the invention is a composition that comprises a radioactive [18F], [123I], [125I], or [131I]-N-radiohaloaryl-alkylcarboxamide molecule. The composition binds to the transient receptor potential-M8 (TRP-M8) receptor of cells. The TRP-M8 receptor is selectively expressed in sensory neurons and in malignant tissues such as prostate cancer cells. The [18F], [123I], [125I], or [131I]-N-radiohaloaryl-alkylcarboxamide ligand may be used for radioreceptor binding studies, for diagnostic studies, and for radiotherapy of cancerous tissues. Affinity of the [125I] or [131I]-N-radiohaloaryl-alkylcarboxamide ligand for the TRP-M8 receptor confers selectivity and specificity in delivering lethal radiation to the diseased cells.

The present invention provides an isolated GABAB receptor protein comprising at least one GABABR1a subunit and at least one GABABR2a subunit, characterized in that said GABAB receptor has one high affinity agonist binding site and one low affinity agonist binding site. In particular the isolated recombinant GABAB receptor protein expressed by the hGABABR1a / GABABR2 CHO cell line deposited at the Belgian Coordinated Collections of Microorganisms (BCCM) as CHO-K1 h-GABA-b R1a / R2 clone on Aug. 22, 2003 with the accession number LMBP 6046CB. It is thus an object of the present invention to provide the hGABABR1a / GABABR2 CHO cell line deposited at the Belgian Coordinated Collections of Microorganisms (BCCM) as CHO-K1 h-GABA-b R1a / R2 clone on Aug. 22, 2003 with the accession number LMBP 6046CB. The invention also provides the use of the aforementioned cell line in a method to identify GABAB receptor agonists using a functional or a binding assay. In particular in a radioligand-binding assay comprising the use of radiolabeled agonists such as for example 3H-GABA or 3H-baclofen. In a particular embodiment the present invention provides the use of the aforementioned GABAB receptor in a method to identify a high affinity GABAB receptor agonist using a functional or a binding assay. In particular in a radioligand-binding assay comprising the use of radiolabeled agonists such as for example 3H-GABA or 3H-baclofen. Alternatively, the aforementioned binding assays are performed on cellular extracts, in particular cellular membrane preparations of the aforementioned cells.

The present disclosure is directed to iterative regularized reconstruction methods. In certain embodiments, the methods incorporate locally-weighted total variation denoising to suppress artifacts induced by PSF modeling. In certain embodiments, the methods are useful for suppressing ringing artifacts while contrast recovery is maintained. In certain embodiments, the weighting scheme can be extended to noisy measures introducing a noise-independent weighting scheme. The present disclosure is also directed to a method for quantifying radioligand binding in a subject without collecting arterial blood. In certain embodiments, the methods incorporate using imaging data and electronic health records to predict one or more anchors, which are used to generate an aterial input function (AIF) for the radioligand.

Compounds having the general formula III′, or IV′wherein R1 can be a radical of an optionally substituted C-4 to C-7 N-containing heterocycle or a radical of an optionally substituted cyclic or acyclic tertiary amine or isoindoline-1,3-dione: R2,4,5,6 can each independently be any one or combinations of the following moieties, cyano, nitro, acyl, alkyl, amido, azido, isothiocyanate, isocyanate, optionally substituted anilino, halogens, ethers, sulfonamides, thioacyl, nitro, aromatic, heterocyclic, olefinic, acetylene, deuterium, or tritium; Y is S; Z can be either H, O, S, S—R or NR where R groups can be either H, aryls, alkyls, or cycloalkyls; “n” can be 1 to 5 carbons in length and stereoisomers, functional analogs, and pharmaceutically acceptable salts thereof and wherein the moiety bridging R1 and N can be a substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene and where the alkylene group can include an inserted C3-C5 cycloalkyl group, aromatic, and heterocyclic group; and wherein X is C1-C4 radiohaloalkyl.

The present specification relates to compositions, devices, apparatuses, methods, kits, and systems for sample preparation (e.g., isolation, reduction, or removal of small molecules from biomolecules in a sample). The molecular weight range lt of exemplary small molecules that can be separated, reduced or removed; 2,000 Da, and may include, but not limited to, dyes, biotins, affinity tags, cross-linkers, reducing agents, labels, nanoparticles, radioligands, mass tags, unreacted molecules, and combinations, intermediates, and derivatives of the foregoing. Exemplary biomolecules present in a sample include, but are not limited to, proteins, glycoproteins, antibodies, peptides, nucleic acids, polysaccharides, carbohydrates, and lipids. The methods, compositions, kits, devices, apparatuses, and systems of the present disclosure can advantageously provide excellent separation of small molecule contaminants and additionally can reduce the time and cost associated with separating small molecules from larger biomolecules in a sample. Isolated biomolecules as shown herein are suitable for better downstream processing.

A method for localizing and quantifying S1R role in nociceptive processing; for providing a guide to providing an analgesic therapy; of using an S1R selective ligand as a biomarker for pathphysiological study of memory deficits and cognitive disorders; or of detecting increased S1R density at the site of nerve injury arising from neuropathic pain comprising using as a probe at least one SR1 selective compound or radioligand of the general formula III′, or IV′: