Washington University

Wenhua Chu

Robert H Mach

Gregory Zipfel

Byung Han

Dong Zhou

Zhude Tu

William G Hawkins

Michael John Welch

Suwanna Vangveravong

Richard S Hotchkiss

Laura Dugan

Rebecca Aft

Mark Mintun

Delphine Chen

Loren Michel

Justin Rothfuss

Robert Mach

The present disclosure relates to the methods for the preparation of reactive [F-18]fluoride in a form of [F-18]sulfonyl fluoride suitable for efficient radiolabeling without an azeotropic evaporation step by the use of anion exchange resin and sulfonyl chloride, and its applications in the manufacturing of PET radiopharmaceuticals.

Synthesizing pet tracers using [F-18]sulfonyl fluoride as a source of [F-18]fluoride

Disclosed are PARP-1 inhibitors, which can beF-labeled for use as tracers in positron emission tomographic (PET) imaging. Further disclosed are methods of synthesis. Of the compounds synthesized, 2-[p-(2-Fluoroethoxy)phenyl]-1.3.10-triazatricyclo[6.4.1.0]trideca-2,4(13),5,7-tetraen-9-one (12) had the highest inhibition potency for PARP-1 (IC=6.3 nM). Synthesis of [F]-12 is disclosed under conventional conditions in high specific activity with 40-50% decay-corrected yield. MicroPET imaging using [F]-12 in MDA-MB-436 tumor-bearing mice demonstrated accumulation of [F]-12 in a tumor. Binding, can be blocked by olaparib. The compounds have utility for tumor imaging.

Radiolabeled tracers for poly (ADP-ribose) polymerase-1 (PARP-1), methods and uses therefor

The present invention encompasses phenoxazine derivatives and methods of use thereof.

Phenoxazine derivatives and methods of use thereof

Tracers for imaging distribution of reactive oxygen species (ROS) are disclosed. The tracers include radiolabeled dihydroethidine (DHE) analogues. Further disclosed are uses of the compounds, including methods of imaging tissue distribution of ROS in vivo by positron emission tomography (PET). Methods of synthesizing the compounds are also disclosed.

Dihydroethidine analogues and uses thereof

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

A series of N-substituted 9-azabicyclo[3.3.1]nonan-3&#x3b1;-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (&#x3c3;1 and &#x3c3;2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3&#x3b1;-yl)-N'-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3&#x3b1;-yl)-N&#x2032;-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for &#x3c3;2 versus &#x3c3;1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the &#x3c3;2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.

Sigma 2 receptor ligands and therapeutic uses therefor

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St. Louis, MO, United States of America

Wenhua Chu