Washington University

Science Research Laboratory, Inc.

Michael John Welch

Robert H Mach

Zhude Tu

Xiaoxu Li

Ruth E Shefer

Robert E Klinkowstein

Dipanjan Pan

Karen L Wooley

Xiankai Sun

Jeremiah J Morrissey, Iv

Raffaella Rossin

Douglas J Rowland

Matthew L Becker

Huafeng Fang

William G Cance

Joseph M Davie

Samuel A Wells, Jr

William G Dilley

Jeffrey L Turner

Barbara J Hughey

Wenhua Chu

John-Stephen Taylor

Pamela K Woodard

Geoffrey E Woodard

Rafaella Rossin

Justin Rothfuss

Douglas J Rowland, Jr

Deborah W McCarthy

John Stephen Taylor

Carmen S Dence

A functional biologically active particle conjugate useful for diagnosis and treating cancer as a bioportal comprises a nanoscale particle having associated therewith an intracellular targeting ligand comprising a PNA, or another nuclease resistant oligonucleotide analog such as MOE-mRNA (2'-methoxyethyl mRNA) or LNA (locked nucleic acid), having a sequence that binds selectively to an uniquely expressed or overexpressed mRNA specific to the cancer or disease state in a living mammal. In one aspect the uniquely overexpressed target specific to the cancer or disease state is the unr mRNA which can be targeted by the antisense sequence PNA50.

Cell permeable nanoconjugates of shell-crosslinked knedel (SCK) and peptide nucleic acids ('PNAs') with uniquely expressed or over-expressed mRNA targeting sequences for early diagnosis and therapy of cancer

Tracers comprising an oligopeptide comprising a fragment of a natriuretic peptide, wherein the fragment comprises the sequence Arg-Ile-Asp-Arg-Ile (SEQ ID NO.: 1), and a signaling moiety, are disclosed. Further disclosed are methods of imaging atherosclerotic plaque by PET scanning or MRI using a tracer.

Natriuretic peptide-mediated imaging of atherosclerotic plaque

Novel isatin analogues, including isatin analogues comprising Michael Acceptors (IMAs) are disclosed. Further disclosed are methods of synthesis of the isatin analogues, and uses of the analogues, including inhibition of caspase-3 and caspase-7, and in vivo imaging of apoptosis by Positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

Isatin analogues and uses therefor

Methods for detection of cancer cells and for determining the proliferative status of cells in a tissue sample in vitro are disclosed. These methods comprise contacting a tissue sample with a radiolabeled compound or salt thereof of Formula wherein at least one of X, Y, and Z comprises a radioisotope, n is an integer from 2 to about 10; and each of A and Ais a C-Calkoxyl, a C-Cfluoroalkyl or a C-Cfluoroalkoxyl. The methods further comprise detecting the distribution of the radioisotope in the tissue sample, whereby a cell having a high density of the radioisotope compared to quiescent cells is diagnostic for a cancer cell.

Detection of cancer cells in vitro using sigma-2 receptor ligands as radiotracers

Novel benzamide compounds of Formula (I), Formula (II), and Formula (III), salts, water soluble salts, analogs and radiolabeled counterparts thereof as sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors. A method for diagnosing a mammal for the presence of a mammalian tumor therein comprises administering to the mammal a diagnostic imaging detectable effective amount of a benzamide compound having a structure illustrated in Formula (I), Formula (II) and Formula (III) and detecting binding of the compound to a tumor in the mammal. A method for diagnostic imaging of a mammalian tissue having cell surface sigma-2 receptors comprising administering to a mammal a diagnostic imaging amount of a compound having a structure illustrated in Formula (I) Formula (II) and Formula (III) and detecting an image of a tissue having an ample cells with sigma-2 receptors.

Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors

Novel benzamide compounds of Formula (I), Formula (II) and Formula (III, salts, water soluble salts, analogs and radiolabeled counterparts thereof as sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors. A method for diagnosing a mammal for the presence of a mammalian tumor therein comprises administering to the mammal a diagnostic imaging detectable effective amount of a benzamide compound having a structure illustrated in Formula (I), Formula (II) and Formula (III) and detecting binding of the compound to a tumor in the mammal. A method for diagnostic imaging of a mammalian tissue having cell surface sigma-2 receptors comprising administering to a mammal a diagnostic imaging amount of a compound having a structure illustrated in Formula (I) Formula (II) and Formula (III) and detecting an image of a tissue having an ample cells with sigma-2 receptors.

Radionuclides are produced according to the present invention at commercially significant yields and at specific activities which are suitable for use in radiodiagnostic agents such as PET imaging agents and radiotherapeutic agents and/or compositions. In the method and system of the present invention, a solid target having an isotopically enriched target layer electroplated on an inert substrate is positioned in a specially designed target holder and irradiated with a charged-particle beam. The beam is preferably generated using an accelerator such as a biomedical cyclotron at energies ranging from about 5 MeV to about 25 MeV. The target is preferably directly irradiated, without an intervening attenuating foil, and with the charged particle beam impinging an area which substantially matches the target area. The irradiated target is remotely and automatically transferred from the target holder, preferably without transferring any target holder subassemblies, to a conveyance system which is preferably a pneumatic or hydraulic conveyance system, and then further transferred to an automated separation system. The system is effective for processing a single target or a plurality of targets. After separation, the unreacted target material can be recycled for preparation of other targets. In a preferred application of the invention, a biomedical cyclotron has been used to produce over 500 mCi of .sup.64 Cu having a specific activity of over 300 mCi/.mu.g Cu according to the reaction .sup.64 Ni(p,n).sup.64 Cu. These results indicate that accelerator-produced .sup.64 Cu is suitable for radiopharmaceutical diagnostic and therapeutic applications.

Production of .sup.64 Cu and other radionuclides using a

A target is bombarded with high energy particles to generate a radioisotope, and the radioisotope is preferably extracted by one of the following: combusting the target in oxygen, stopping the bombardment and heating the target, or heating the target by induction. Bombardment may take place through a windowless path, and the radioisotope may be used for PET. The particles used may be deuterons or protons, and .sup.13 N may be generated. .sup.11 C may also be generated from either .sup.11 B or .sup.10 B using protons or deuterons. Combustion may be performed by induction heating and may be controlled by the quantity of oxygen available or the temperature. Combustion may be primarily confined to a surface layer and the target may be reused. The beam energy may be 2.2 MeV or less. Another general aspect includes trapping the oxides of .sup.13 N in a trap. The oxides may be converted into .sup.13 N-Ammonia, and this conversion may take place in the trap, which trap may comprise silica gel and sodium hydroxide and may also contain a reducing agent such as Raney-Nickel.

Method for producing radioisotopes

Monoclonal antibodies specific for an antigen present on the surface of parathyroid tissue are useful in imaging such tissue when conjugated to suitable label. The antibodies of the invention bind exclusively to parathyroid surfaces and do not bind to other tissues. The antibodies are useful in establishing the location of the parathyroid whether in its normal location or in ectopic placements. An exemplary monoclonal has been deposited at the American Type Culture Collection and has accession number ATCC No. HB9917.

Monoclonal antibodies and cell lines for parathyroid tissue-specific

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Clayton, MO, United States of America

Michael John Welch