University of California

Other

Jorge R Barrio

Nagichettiar Satyamurthy

Gary W Small

Sung-Cheng Huang

Mohammad Namavari

R Michael Van Dam

Sebastian Olma

Mark Eddings

Clifton Kwang-Fu Shen

Gregory M Cole

Michael E Phelps

Bernard Amarasekera

Andrej Petric

Dirk Williams

Jie Liu

Allyson J Bishop

Vladimir Kepe

Ernest M Wright

Bruce A Hirayama

Tatsushi Toyokuni

Harvey R Herschman

Koon-Pong Wong

Gerald T Bida

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

A method of using PET imaging includes using PET images obtained using a radiotracer for the determination of the progressive course of regional brain PET activities for a progressive neurodegenerative disease (e.g., MCI, AD, and CTE). The method may be used for the automatic staging of neurodegenerative disease for a particular patient/subject based on regional intensity and spatial patterns of the brain signals measured by PET imaging. The method may also be used to diagnose or classify the disease of a patient among multiple possibilities based on PET imaging profiles (e.g., for separating or distinguishing CTE from AD).

Method for positron emission tomography (PET) imaging analysis for classifying and diagnosing of neurological diseases

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

Radiolabeled tracers for sodium/glucose cotransporters (SGLTs), their synthesis, and their use are provided. The tracers are methyl or ethyl pyranosides having an equatorial hydroxyl group at carbon-2 and a C 1 preferred conformation, radiolabeled withF,I, orI, or free hexoses radiolabeled withF,I, or. Also provided are in vivo and in vitro techniques for using these and other tracers as analytical and diagnostic tools to study glucose transport, in health and disease, and to evaluate therapeutic interventions.

Tracers for monitoring the activity of sodium/glucose cotransporters in health and disease

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

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

A method for labeling &bgr;-amyloid plaques and neurofibrillary tangles in vivo and in vitro, comprises contacting a compound of formula (I):

An efficient, regiocontrolled approach to the synthesis of 8-fluoropurines by direct fluorination of purines with dilute elemental fluorine, or acetyl hypofluorite, is provided. In a preferred embodiment, a purine compound is dissolved in a polar solvent and reacted with a dilute mixture of F,in He or other inert gas.

Growing community of inventors

Agoura Hills, CA, United States of America

Jorge R Barrio