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Title: 211-astatine containing radiotherapeutics for the treatment of cancer

Patent ·
OSTI ID:1600218
; ; ;

Described herein is an alpha-emitting radionuclide, 211At, which has been incorporated into a selective sigma-2 ligand moiety to provide cytotoxic capabilities to a chemical compound. As described herein, a compound of formula (I), wherein R1-R4, m, and n are defined herein, was prepared and utilized in in vitro and in vivo tumor targeting of alpha-emitting sigma-2 ligand in a breast cancer model. In one embodiment, the compound is 5-(211At)—N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2,3-dimethoxybenzamide.

Research Organization:
Univ. of Pennsylvania, Philadelphia, PA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
DOE Contract Number:
SC0012476
Assignee:
The Trustees of the University of Pennsylvania (Philadelphia, PA)
Patent Number(s):
10,457,642
Application Number:
15/571,055
OSTI ID:
1600218
Resource Relation:
Patent File Date: 04/26/2016
Country of Publication:
United States
Language:
English

References (65)

Detection of Cancer Cells in Vitro Using Sigma-2 Receptor Ligands as Radiotracers patent-application February 2010
Use of Multifunctional Sigma-2 Receptor Ligand Conjugates to Trigger Cancer-Selective Cell Death Signaling journal January 2012
Dihydroethidine Analogues and Uses Thereof patent-application March 2013
Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site journal July 2011
Detection of cancer cells in vitro using sigma-2 receptor ligands as radiotracers patent February 2011
Targeted Alpha-Particle Immunotherapy for Acute Myeloid Leukemia journal May 2014
Compounds Comprising 4-Benzoylpiperidine as a Sigma-1-Selective Ligand patent-application December 2011
Phenoxazine Derivatives and Methods of Use Thereof patent-application February 2012
1H-[1,2,3] Triazole Substituted Amino Acids and Uses Thereof patent-application November 2010
Effect of structural modification in the amine portion of substituted aminobutyl-benzamides as ligands for binding σ1 and σ2 receptors journal March 2011
The σ2 Receptor: A Novel Protein for the Imaging and Treatment of Cancer journal June 2013
Functional assays to define agonists and antagonists of the sigma-2 receptor journal March 2014
[18F]N-4′-Fluorobenzyl-4-(3-bromophenyl) acetamide for imaging the sigma receptor status of tumors: comparison with [18F]FDG and [125I]IUDR journal May 2001
Subcellular Localization of Sigma-2 Receptors in Breast Cancer Cells Using Two-Photon and Confocal Microscopy journal July 2007
Production of [ 211 At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy journal February 2013
Radiolabelled Benzamide Analogues, Their Synthesis and Use in Diagnostic Imaging patent-application May 2008
Fluorine-18-Labeled Benzamide Analogues for Imaging the σ2 Receptor Status of Solid Tumors with Positron Emission Tomography journal June 2007
Sigma 2 receptor ligands and therapeutic uses therefor patent November 2009
Radiolabelled Benzamide Analogues, Their Synthesis and Use in Diagnostic Imaging patent-application June 2010
Sigma 2 Receptor Ligands and Therapeutic Uses Therefor patent-application July 2008
Synthesis and Characterization of [125I]-N-(N-Benzylpiperidin-4-yl)-4-iodobenzamide, a New .sigma. Receptor Radiopharmaceutical: High-Affinity Binding to MCF-7 Breast Tumor Cells journal June 1994
[211At]Astatine-Labeled Compound Stability: Issues with Released [211At]Astatide and Development of Labeling Reagents to Increase Stability journal September 2008
Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors patent June 2008
Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors patent November 2009
Isatin Analogues and Uses Therefor patent-application March 2009
Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer journal July 2013
Compositions and Methods for Treating Neurodegenerative Disease patent-application December 2014
Synthesis of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl carbamate analogs as σ2 receptor ligands journal October 2006
Modular Platform for Targeted Therapeutic Delivery patent-application July 2009
Potential applications for sigma receptor ligands in cancer diagnosis and therapy journal October 2015
Pet Radiotracers for Imaging Fatty Acid Metabolism and Storage patent-application April 2012
Targeted pancreatic cancer therapy with the small molecule drug conjugate SW IV‐134 journal March 2014
Conformationally-flexible benzamide analogues as dopamine D3 and σ2 receptor ligands journal January 2004
Pegylated Fluorobenzamide Analogues, Their Synthesis and Use in Diagnostic Imaging patent-application July 2012
Radiolabeled 2-Amino-4-Alkyl-6-(Haloalkyl)pyridine Compounds and Their Use in Diagnostic Imaging patent-application November 2010
New N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs as σ2 receptor ligands: Synthesis, in vitro characterization, and evaluation as PET imaging and chemosensitization agents journal February 2009
Tricyclic Heteroaromatic Compounds as Alpha-Synuclein Ligands patent-application November 2013
1 H-[1, 2, 3] triazole substituted amino acids and uses thereof patent May 2014
Radiolabelled benzamide analogues, their synthesis and use in diagnostic imaging patent May 2011
Compounds, compositions, and methods for cancer imaging and therapy patent July 1999
Therapeutic uses of bicyclic ligands of sigma 2 receptor patent May 2012
Sigma-2 receptor ligands potentiate conventional chemotherapies and improve survival in models of pancreatic adenocarcinoma journal March 2009
Assessment of Cellular Proliferation in Tumors by PET Using 18 F-ISO-1 journal January 2013
Radiolabelled fluorobenzamide analogues, their synthesis and use in diagnostic imaging patent June 2012
Phenoxazine derivatives and methods of use thereof patent May 2014
Isatin analogues and uses therefor patent December 2012
Sigma-2 Receptor Radiotracers for Imaging the Proliferative Status of Solid Tumors patent-application May 2005
Biodistribution and Dosimetry of Free 211At, 125I− and 131I− in Rats journal November 2013
Conjugation to a SMAC mimetic potentiates sigma-2 ligand induced tumor cell death in ovarian cancer journal March 2014
Characterization of a novel iodinated sigma-2 receptor ligand as a cell proliferation marker journal February 2006
Compounds comprising 4-benzoylpiperidine as a sigma-1-selective ligand patent February 2014
Carbon-11 labeled σ2 receptor ligands for imaging breast cancer journal July 2005
Sigma-2 receptors as a biomarker of proliferation in solid tumours journal March 2000
Modular platform for targeted therapeutic delivery patent March 2012
Sigma-2 ligands induce tumour cell death by multiple signalling pathways journal January 2012
Radiotoxicity of Bismuth-213 Bound to Membranes of Monolayer and Spheroid Cultures of Tumor Cells journal March 1999
The novel sigma-2 receptor ligand SW43 stabilizes pancreas cancer progression in combination with gemcitabine journal November 2010
Rat liver and kidney contain high densities of σ1 and σ2 receptors: characterization by ligand binding and photoaffinity labeling journal June 1994
Radiolabelled benzamide analogues, their synthesis and use in diagnostic imaging patent February 2010
Radiolabelled Fluorobenzamide Analogues, Their Synthesis and Use in Diagnostic Imaging patent-application September 2011
Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells journal October 1999
Therapeutic Uses of Bicyclic Ligands of Sigma 2 Receptor patent-application February 2010
Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for treating ovarian cancer journal October 2013
Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy journal July 2007
Pegylated fluorobenzamide analogues, their synthesis and use in diagnostic imaging patent August 2013

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