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Office of Scientific and Technical Information
 

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
Country of Publication:
United States
Language:
English

References (32)

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Rat liver and kidney contain high densities of σ1 and σ2 receptors: characterization by ligand binding and photoaffinity labeling journal June 1994
Sigma-2 receptors as a biomarker of proliferation in solid tumours journal March 2000
[211At]Astatine-Labeled Compound Stability: Issues with Released [211At]Astatide and Development of Labeling Reagents to Increase Stability journal September 2008
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Targeted pancreatic cancer therapy with the small molecule drug conjugate SW IV‐134 journal March 2014
Assessment of Cellular Proliferation in Tumors by PET Using 18 F-ISO-1 journal January 2013
Biodistribution and Dosimetry of Free 211At, 125I− and 131I− in Rats journal November 2013
Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site journal July 2011
Production of [ 211 At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy journal February 2013
Sigma-2 receptor ligands potentiate conventional chemotherapies and improve survival in models of pancreatic adenocarcinoma journal March 2009
Effect of structural modification in the amine portion of substituted aminobutyl-benzamides as ligands for binding σ1 and σ2 receptors journal March 2011
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Subcellular Localization of Sigma-2 Receptors in Breast Cancer Cells Using Two-Photon and Confocal Microscopy journal July 2007
The σ2 Receptor: A Novel Protein for the Imaging and Treatment of Cancer journal June 2013
The novel sigma-2 receptor ligand SW43 stabilizes pancreas cancer progression in combination with gemcitabine journal November 2010
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Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy journal July 2007
Conjugation to a SMAC mimetic potentiates sigma-2 ligand induced tumor cell death in ovarian cancer journal March 2014
Fluorine-18-Labeled Benzamide Analogues for Imaging the σ2 Receptor Status of Solid Tumors with Positron Emission Tomography journal June 2007
Targeted Alpha-Particle Immunotherapy for Acute Myeloid Leukemia journal May 2014
Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer journal July 2013
Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for treating ovarian cancer journal October 2013
Conformationally-flexible benzamide analogues as dopamine D3 and σ2 receptor ligands journal January 2004
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Radiotoxicity of Bismuth-213 Bound to Membranes of Monolayer and Spheroid Cultures of Tumor Cells journal March 1999
Sigma-2 ligands induce tumour cell death by multiple signalling pathways journal January 2012
Characterization of a novel iodinated sigma-2 receptor ligand as a cell proliferation marker journal February 2006

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62 RADIOLOGY AND NUCLEAR MEDICINE