University of California

University of Illinois

Other

Nagichettiar Satyamurthy

Jorge R Barrio

Caius G Radu

Gary W Small

Mohammad Namavari

R Michael Van Dam

Jennifer Marie Murphy

Mark Eddings

Sebastian Olma

Gregory M Cole

Clifton Kwang-Fu Shen

David A Nathanson

Sung-Cheng Huang

Michael E Phelps

Bernard Amarasekera

Dirk Williams

Andrej Petric

Jue Wang

Michael E Jung

Arnon Lavie

Johannes Czernin

Zheng Li

Jie Liu

Raymond M Gipson

Allyson J Bishop

Owen N Witte

Vladimir Kepe

Gerald T Bida

Harvey R Herschman

Tatsushi Toyokuni

Chengyi J Shu

Evan David Nair-Gill

Hsiang-I Liao

A method of manufacturing 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)-malononitrile ([F-18]FDDNP) utilizes a semi-automated module that is used to perform fluorination, pre-purification, separation, product extraction, and formulation. The method is able to produce [F-18]FDDNP with high yields and ready for human administration under existing FDA regulations, and without the need for hazardous organic solvents such as dichloromethane (DCM), methanol (MeOH), and tetrahydrofuran (THF). The method also improves the speed with which [F-18]FDDNP can be synthesized with the method being able to generate a final product within about 90 to 100 minutes. This synthesis method is easily adaptable to FDA registered and approved automated synthesis systems.

Methods for multi-dose synthesis of [F-18]FDDNP for clinical settings

Provided herein are compounds that bind to dCK and methods for treating cancer.

Deoxycytidine kinase inhibitors

The invention provides compounds that bind to deoxycytidine kinase (dCK) and compositions including pharmaceutically acceptable compositions containing the compounds. The compounds are useful in treating diseases and disorders where dCK activity is implicated such as cancer and immune disorders. The compounds also find use in clinical methodologies including positron emission tomography (PET) imaging.

Deoxycytidine kinase binding compounds

A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

Modular radiochemistry synthesis system

Phenyliodonium ylide derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are shown for use as precursors in aromatic nucleophilic substitution reactions. The iodonium ylide group is substituted by nucleophiles such as halide ions to provide the corresponding haloaryl derivatives. No-carrier-added [F-18]fluoride ion exclusively substitutes the iodonium ylide moiety in these derivatives and provides high specific activity F-18 labeled fluoro derivatives. Protected L-dopa-6-iodonium ylide derivative have been synthesized as a precursors for the preparation of no-carrier-added 6-[F-18]fluoro-L-dopa. The iodonium ylide group in this L-dopa.derivative is nucleophilically substituted by no-carrier-added [F-18]fluoride ion to provide a [F-18]fluoro intermediates which upon acid hydrolysis yielded 6-[F-18]fluoro-L-dopa.

No-carrier-added nucleophilic [F-18] fluorination of aromatic compounds

Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18]fluoride ion derived from anhydrous [F-18](F/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., MeNF, EtNF, n-BuNF, (PhCH)NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F-18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

Nucleophilic fluorination of aromatic compounds

Radiolabeled tracers for sulfotransferases (SULTs), their synthesis, and their use are provided. Included are substituted phenols, naphthols, coumarins, and flavones radiolabeled withF,I,I,I, orC. Also provided are in vivo techniques for using these and other tracers as analytical and diagnostic tools to study sulfotransferase distribution and activity, in health and disease, and to evaluate therapeutic interventions.

In vivo imaging of sulfotransferases

Compounds for use as PET probes and methods for synthesizing and using these, comprising [F]D-FAC and other cytosine and adenosine analogs.

Positron emission tomography probes for imaging immune activation and selected cancers

Compositions useful for labeling &#x3b2;-amyloid plaques and neurofibrillary tangles are provided. The compositions comprises compounds of formula (I): wherein Ris selected from the group consisting of &#x2014;C(O)-alkyl, &#x2014;C(O)-alkylenyl-R, &#x2014;C(O)O-alkyl, &#x2014;C(O)O-alkylenyl-R, &#x2014;C&#x2550;C(CN)-alkyl, &#x2014;C&#x2550;C(CN)-alkylenyl-R, wherein Ris a radical selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl; Ris a radical selected from the group consisting of &#x2014;NH, &#x2014;OH, &#x2014;SH, &#x2014;NH-alkyl, &#x2014;NHR, &#x2014;NH-alkylenyl-R, &#x2014;O-alkyl, &#x2014;O-alkylenyl-R, &#x2014;S-alkyl, and &#x2014;S-alkylenyl-R; Ris a radical selected from the group consisting of &#x2014;CN, &#x2014;COOH, &#x2014;C(O)O-alkyl, &#x2014;C(O)O-alkylenyl-R, &#x2014;C(O)-alkyl, &#x2014;C(O)-alkylenyl-R, &#x2014;C(O)-halogen, &#x2014;C(O)NH-alkyl, &#x2014;C(O)NH-alkylenyl-Rand &#x2014;C(O)NH; Ris a radical selected from the group consisting of O, NH, and S; and Ris N, O or S; and Ris selected from the group consisting of alkyl and alkylenyl-Rand Ris alkylenyl-R, wherein Ris selected from the group consisting of &#x2014;OH, &#x2014;OTs, halogen, spiperone, spiperone ketal, and spiperone-3-yl, or Rand Rtogether form a heterocyclic ring, optionally substituted with at least one radical selected from the group consisting of alkyl, alkoxy, OH, OTs, halogen, alkyl-R, carbonyl, spiperone, spiperone ketal and spiperone-3-yl, and further wherein one or more of the hydrogen, halogen or carbon atoms are optionally replaced with a radiolabel.

Compositions for labeling &#x3b2;-amyloid plaques and neurofibrillary tangles

This invention provides novel cyclooxygenase-2 selective agents that are particularly useful as imaging probes in non-invasive imaging techniques, such as PET and SPECT. Preferred cyclooxygenase-2 selective agents inhibit cyclooxygenase-2 activity with greater potency and specificity than conventional cyclooxygenase-2 inhibitors. Other aspects of the invention include pharmaceutical compositions including the cyclooxygenase-2 selective agents as well as methods for detecting and/or inhibiting cyclooxygenase-2. These methods are particularly useful for diagnosing and treating disorders, such as inflammation, which is characterized by elevated cyclooxygenase-2 levels.

Cyclooxygenase-2 selective agents useful as imaging probes and related methods

Methods for labeling &bgr;-amyloid plaques and neurofibrillary tangles

Growing community of inventors

Los Angeles, CA, United States of America

Nagichettiar Satyamurthy