Abstract: The present application discloses compositions and methods of synthesis and use of 18F or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.

Abstract: The present invention provides for a process for preserving biological material. The process comprises subjecting the biological material to a fixation process and then packaging the biological material in a container under a controlled atmosphere of noble gas. In the process, the controlled atmosphere of noble gas utilized comprises one or more noble gases selected from argon, xenon, helium, neon, krypton and radon. The process optionally also utilizes one or more additional gases selected from nitric oxide, hydrogen, hydrogen sulfide, carbon monoxide, carbon dioxide, nitrogen and oxygen. This process allows for the long term storage of the biological material.

Abstract: Disclosed herein is a method for the preparation of radioisotope-labeled compounds using CNT. It comprises filling the carbon nanotube with a radioisotope; and labeling a physiologically active material with the radioisotope charged in the carbon nanotube. Taking advantage of CNT, the method can prepare a radioisotope-labeled compound invention at a high yield and in a simple manner. Also, the radioisotope, when remaining unreacted, can be recovered by the filtration of the CNT, thereby achieving the prevention of radioactive contamination and the reduction of radioactive waste. Further, the radioisotope-labeled compound is useful as a contrast medium for imaging the hepatobiliary system.

Abstract: This invention relates to a group of novel chelating agents, novel chelates, biomolecules labeled with said chelates or chelating agents as well as solid supports conjugated with said chelates, chelating agents or labeled biomolecules. Especially the invention relates to novel chelating agents useful in solid phase synthesis of oligonucleotides or oligopeptides and the oligonucleotides and oligopeptides so obtained.

Abstract: The present invention is directed to metal chelating conjugates for use as metallopharmaceutical diagnostic or therapeutic agents. Specifically, conjugates of the present invention include one or more carriers, a linker, and metal coordinating moiety comprising a resorcinol, thioresorcinol, or dithioresorcinol derivative through which the metal coordinating moiety is bonded to the linker.

Abstract: Use of benzimidazole-derived compounds of formula (I) according to the following structure, wherein x is a heteroatom selected from N, S, O, P, SO, SO2 and SO3, preferably from N, S and SO3 and most preferably from N and SO3; n may be 0 or 1, R1 is a group selected from formula (II) and formula (III) and R2 is a group selected from H and formula (IV) since the aforesaid serves for the production of a formulation used as a specific marker in the case of neurodegenerative diseases and tau pathologies.

Abstract: In certain embodiments, methods of the present invention obtain dynamic data sets of an NMR spectroscopy signal of polarized 129Xe in a selected structure, environment, or system. The signal data can be used to evaluate: (a) the physiology of a membrane or tissue; (b) the operational condition or function of a body system or portion thereof (when at rest or under stimulation); and/or (c) the efficacy of a therapeutic treatment used to treat a diagnosed disorder, disease, or condition. Thus, the present invention provides methods for screening and/or diagnosing a respiratory, cardiopulmonary disorder or disease such as chronic heart failure, and/or methods for monitoring the efficacy of therapeutics administered to subject to treat the disorder or disease.

Abstract: The invention provides compositions and methods for therapeutic and diagnostic applications.

Abstract: In certain embodiments, methods of the present invention obtain dynamic data sets of an NMR spectroscopy signal of polarized 129Xe in a selected structure, environment, or system. The signal data can be used to evaluate: (a) the physiology of a membrane or tissue; (b) the operational condition or function of a body system or portion thereof (when at rest or under stimulation); and/or (c) the efficacy of a therapeutic treatment used to treat a diagnosed disorder, disease, or condition. Thus, the present invention provides methods for screening and/or diagnosing a respiratory, cardiopulmonary disorder or disease such as chronic heart failure, and/or methods for monitoring the efficacy of therapeutics administered to subject to treat the disorder or disease.

Abstract: A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

Abstract: The present invention describes novel compounds of the formula: (Q)d-Ln-Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention further provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia and myocardial reperfusion injury. The present invention still further provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety.

Abstract: Stable isotope labeling and neutron activation to measure biological functions are provided, as are the use and method of adding a chemical monitor to correct for neutron flux to sample vials prior to the addition of sample is presented, and the use of stable isotopes as a chemical bar code for vials and other items. Methods are provided also for measuring glomerular filtration rate and glomerular sieving function in a subject, and for measuring other physiological functions.

Abstract: The present invention provides an ?-particle-emitting radioisotope chelation complex comprising 225Actinium (225Ac) and 1,4,7,10,13,16-hexaazacyclohexadecane-N,N?,N?,N?,N?,N?-hexaacetic acid (HEHA) (225Ac-HEHA). Also provided is a bifunctional HEHA, and a bifunctional 225Ac-HEHA. The bifunctional HEHA and the bifunctional 225Ac-HEHA can be conjugated to a targeting agent. In view of the above, the present invention provides a method of making HEHA and methods of making a bifunctional HEHA, including a conjugate thereof. Also provided are a method of treating disease, a method of treating cancer, a method of decontaminating a sample from 225Ac, a method of decontaminating a person who has been externally contaminated with 225Ac, and a method of detoxifying a person who has internalized 225Ac.

Abstract: MR spectroscopy and imaging methods for imaging pulmonary and cardiac vasculature and the cardiac region and evaluating blood flow or circulatory deficits use dissolved phase polarized 129Xe gas and large flip angle excitation pulses. Pulmonary and cardiac vasculature MRI images are obtained by delivering gas to a patient via inhalation such as with a breath-hold delivery-procedure, exciting the dissolved phase gas with a large flip angle pulse, and generating a corresponding image. Preferably, the image is obtained using multi-echo imaging techniques. Blood flow is quantified using low field MR spectroscopy and an RF excitation pulse with a frequency which corresponds to the resonance of the dissolved phase 129Xe.

Abstract: The present invention provides an &agr;-particle-emitting radioisotope chelation complex comprising 225Actinium (225Ac) and 1,4,7,10,13,16-hexaazacyclohexadecane-N,N′,N″,N′″,N″″,N′″″-hexaacetic acid (HEHA) (225Ac-HEHA). Also provided is a bifunctional HEHA, and a bifunctional 225Ac-HEHA. The bifunctional HEHA and the bifunctional 225Ac-HEHA can be conjugated to a targeting agent. In view of the above, the present invention provides a method of making HEHA and methods of making a bifunctional HEHA, including a conjugate thereof. Also provided are a method of treating disease, a method of treating cancer, a method of decontaminating a sample from 225Ac, a method of decontaminating a person who has been externally contaminated with 225Ac, and a method of detoxifying a person who has internalized 225Ac.

Abstract: A compound for use as a diagnostic or therapeutic pharmaceutical and method of using the same where the compound consists essentially of an alpha-melanotropin stimulating hormone analog which has integrally located a radionuclide. The radionuclide is administered to the body in an amount sufficient to allow uptake and retention by the tumor cells.

Abstract: This invention describes the use of metal complexes that have a plasma protein bond of at least 10% as imaging diagnostic agents for locating an infarction or a necrosis using lasting positive visualization.

Abstract: MR spectroscopy and imaging methods for imaging pulmonary and cardiac vasculature and the cardiac region and evaluating blood flow or circulatory deficits use dissolved phase polarized 129Xe gas and large flip angle excitation pulses. Pulmonary and cardiac vasculature MRI images are obtained by delivering gas to a patient via inhalation such as with a breath-hold delivery -procedure, exciting the dissolved phase gas with a large flip angle pulse, and generating a corresponding image. Preferably, the image is obtained using multi-echo imaging techniques. Blood flow is quantified using low field MR spectroscopy and an RF excitation pulse with a frequency which corresponds to the resonance of the dissolved phase 129Xe.

Abstract: Methods for increasing the T1 of injectable microbubble formulations of hyperpolarized 3He include the step of introducing the hyperpolarized 3He to a quantity of microbubbles held in a chamber and increasing the pressure therein to facilitate the movement or loading of the 3He into the microbubbles. Subsequently, a limited quantity of carrier liquid or a carrier liquid solution alone, or pre-mixed with 3He, can be introduced to the microbubble/3He in the chamber to inhibit the tendency of the 3He to leach out of the bubble. Related pharmaceutical products and associated containers as well as an evacuation based method for rapid mixing and delivery of the bubbles and the 3He is also disclosed. An additional method for dissolving 129Xe gas by using bubbles as an accelerant is also described.

Abstract: The invention relates to macrocyclic perfluoroalkylamides, their production and their use in diagnosis.

Abstract: Novel methods, processes and metal complexes attached to a hypoxia-localizing moiety comprising a metal, preferably radionuclide of rhenium or technetium; a hypoxia-localizing moiety; and, a complexing ligand, wherein said ligand and said radionuclide combined have cell membrane permeabilities greater than that of sucrose, are disclosed.

Abstract: A compound for use as a diagnostic or therapeutic pharmaceutical and method of using the same where the compound consists essentially of an alpha-melanotropin stimulating hormone analog which has integrally located a radionuclide. The radionuclide is administered to the body in an amount sufficient to allow uptake and retention by the tumor cells.

Abstract: Cascade polymers, containing complex-forming ligands, optionally at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83, as well as, if desired, cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable complexing compounds and complexes for diagnostics and therapy.

Abstract: The invention relates to compounds useful as radiosensitizers in tumor therapy.

Abstract: Methods for increasing the T1 of injectable microbubble formulations of hyperpolarized 3He include the step of introducing the hyperpolarized 3He to a quantity of microbubbles held in a chamber and increasing the pressure therein to facilitate the movement or loading of the 3He into the microbubbles. Subsequently, a limited quantity of carrier liquid or a carrier liquid solution alone, or pre-mixed with 3He, can be introduced to the microbubble/3He in the chamber to inhibit the tendency of the 3He to leach out of the bubble. Related pharmaceutical products and associated containers as well as an evacuation based method for rapid mixing and delivery of the bubbles and the 3He is also disclosed. An additional method for dissolving 129Xe gas by using bubbles as an accelerant is also described.

Abstract: Diagnostic and therapeutic compositions in the form of complexes for enhancing transmembrane transport of a diagnostic or therapeutic agent and methods for their use. The complexes contain the &agr;, &ggr;, or bis isomers of folate receptor-binding analogs of folate, a metal chelated by a ligand, and in one embodiment, a chemotherapeutic agent.

Abstract: A method of imaging a spatial distribution of a noble gas by nuclear magnetic resonance spectrometry includes detecting a spatial distribution of at least one noble gas by NMR spectrometry and generating a representation of said spatial distribution of the noble gas. The noble gas is selected from noble gas isotopes having nuclear spin, preferably Xenon-129 and/or Helium-3. The noble gas is at least thermally or equilibrium polarized and is preferably hyperpolarized, most preferably hyperpolarized by optical (laser) pumping in the presence of an alkali metal or by metastability exchange. The generation of the representation of the noble gas spatial distribution includes at least one dimension, preferably 2 or 3 dimensions of the spatial distribution. The noble gas may be imaged according to the invention in chemical or biological systems, preferably in a human or animal subject or organ system or tissue thereof.

Abstract: A method of imaging a spatial distribution of a noble gas by nuclear magnetic resonance spectrometry includes detecting a spatial distribution of at least one noble gas by NMR spectrometry and generating a representation of said spatial distribution of the noble gas. The noble gas is selected from noble gas isotopes having nuclear spin, preferably Xenon-129 and/or Helium-3. The noble gas is at least thermally or equilibrium polarized and is preferably hyperpolarized, most preferably hyperpolarized by optical (laser) pumping in the presence of an alkali metal or by metastability exchange. The generation of the representation of the noble gas spatial distribution includes at least one dimension, preferably 2 or 3 dimensions of the spatial distribution. The noble gas may be imaged according to the invention in chemical or biological systems, preferably in a human or animal subject or organ system or tissue thereof.

Abstract: This invention relates to therapeutic reagents and peptides, including radiotherapeutic reagents and peptides, radiodiagnostic reagents and peptides, and methods for producing labeled radiodiagnostic agents. Specifically, the invention relates to cyclic peptide derivatives and analogs of somatostatin, and embodiments of such peptides radiolabeled with a radioisotope, as well as methods and kits for making, radiolabeling and using such peptides for radiodiagnostic and radiotherapeutic purposes. The invention specifically relates to cyclic peptide derivatives and analogues of somatostatin radiolabeled with technetium-99m and uses thereof as scintigraphic imaging agents. The invention also specifically relates to cyclic peptide derivatives and analogues of somatostatin radiolabeled with cytotoxic radioisotopes such as rhenium-186 (186Re) and rhenium-188 (188Re) for use as radiotherapeutic agents.

Abstract: A method of imaging a spatial distribution of a noble gas by nuclear magnetic resonance spectrometry includes detecting a spatial distribution of at least one noble gas by NMR spectrometry and generating a representation of said spatial distribution of the noble gas. The noble gas is selected from noble gas isotopes having nuclear spin, preferably Xenon-129 and/or Helium-3. The noble gas is at least thermally or equilibrium polarized and is preferably hyperpolarized, most preferably hyperpolarized by optical (laser) pumping in the presence of an alkali metal or by metastability exchange. The generation of the representation of the noble gas spatial distribution includes at least one dimension, preferably 2 or 3 dimensions of the spatial distribution. The noble gas may be imaged according to the invention in chemical or biological systems, preferably in a human or animal subject or organ system or tissue thereof.

Abstract: A peptide-chelator conjugate that is useful for imaging sites of inflammation in humans comprises a metal chelator coupled to a glycopeptide antibiotic. The metal chelator and the glycopeptide are coupled by a linking group. The linking group may be the divalent radical NH--(CH.sub.2).sub.3 --NH. Alternatively the linking group may be .beta.Ala.sub.3 LysGly-OH and the glycopeptide may be coupled to the N.sup..epsilon. of Lys. A method of imaging a site of inflammation is also provided. The method comprises the step of administering a diagnostically effective amount of a composition comprising a glycopeptide-chelator conjugate comprising a metal chelator coupled to a glycopeptide antibiotic. The glycopeptide-chelator conjugate is in a form complexed with a diagnostically useful metal or an oxide or nitride thereof.

Abstract: A method of imaging a spatial distribution of a noble gas by nuclear magnetic resonance spectrometry includes detecting a spatial distribution of at least one noble gas by NMR spectrometry and generating a representation of said spatial distribution of the noble gas. The noble gas is selected from noble gas isotopes having nuclear spin, preferably Xenon-129 and/or Helium-3. The noble gas is at least thermally or equilibrium polarized and is preferably hyperpolarized, most preferably hyperpolarized by optical (laser) pumping in the presence of an alkali metal or by metastability exchange. The generation of the representation of the noble gas spatial distribution includes at least one dimension, preferably 2 or 3 dimensions of the spatial distribution. The noble gas may be imaged according to the invention in chemical or biological systems, preferably in a human or animal subject or organ system or tissue thereof.

Abstract: A method of imaging a spatial distribution of a noble gas by nuclear magnetic resonance spectrometry includes detecting a spatial distribution of at least one noble gas by NMR spectrometry and generating a representation of said spatial distribution of the noble gas. The noble gas is selected from noble gas isotopes having nuclear spin, preferably Xenon-129 and/or Helium-3. The noble gas is at least thermally or equilibrium polarized and is preferably hyperpolarized, most preferably hyperpolarized by optical (laser) pumping in the presence of an alkali metal or by metastability exchange. The generation of the representation of the noble gas spatial distribution includes at least one dimension, preferably 2 or 3 dimensions of the spatial distribution. The noble gas may be imaged according to the invention in chemical or biological systems, preferably in a human or animal subject or organ system or tissue thereof.

Abstract: This invention relates to a method of imaging amyloid deposits and to labeled compounds, and methods of making labeled compounds useful in imaging amyloid deposits. This invention also relates to compounds, and methods of making compounds for inhibiting the aggregation of amyloid proteins to form-amyloid deposits, and a method of delivering a therapeutic agent to amyloid deposits.