211-astatine containing radiotherapeutics for the treatment of cancer

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

Abstract

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.

Inventors:: Pryma, Daniel A.; Lieberman, Brian P.; Makvandi, Mehran; Mach, Robert H.

Issue Date:: 2019-10-29

Research Org.:: Univ. of Pennsylvania, Philadelphia, PA (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

OSTI Identifier:: 1600218

Patent Number(s):: 10457642

Application Number:: 15/571,055

Assignee:: The Trustees of the University of Pennsylvania (Philadelphia, PA)

Patent Classifications (CPCs):: A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

G - PHYSICS G21 - NUCLEAR PHYSICS G21H - OBTAINING ENERGY FROM RADIOACTIVE SOURCES

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A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K41/0038 - {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy

G - PHYSICS G21 - NUCLEAR PHYSICS G21H - OBTAINING ENERGY FROM RADIOACTIVE SOURCES
G21H5/02 - as tracers

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K51/0446 - {having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil}

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P35/00 - Antineoplastic agents

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61N - ELECTROTHERAPY
A61N5/10 - X-ray therapy

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K51/0455 - {having six-membered rings with one nitrogen as the only ring hetero atom}
A61K45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07D - HETEROCYCLIC COMPOUNDS
C07D209/44 - Iso-indoles
C07D217/04 - with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K9/0019 - {Injectable compositions

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DOE Contract Number:: SC0012476

Resource Type:: Patent

Resource Relation:: Patent File Date: 04/26/2016

Country of Publication:: United States

Language:: English

Citation Formats


                    Pryma, Daniel A., Lieberman, Brian P., Makvandi, Mehran, and Mach, Robert H. 211-astatine containing radiotherapeutics for the treatment of cancer.  United States: N. p., 2019. 
        Web.

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                    Pryma, Daniel A., Lieberman, Brian P., Makvandi, Mehran, & Mach, Robert H. 211-astatine containing radiotherapeutics for the treatment of cancer.  United States.

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                    Pryma, Daniel A., Lieberman, Brian P., Makvandi, Mehran, and Mach, Robert H. Tue .  
        "211-astatine containing radiotherapeutics for the treatment of cancer".  United States.  https://www.osti.gov/servlets/purl/1600218.

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@article{osti_1600218,

  title        = {211-astatine containing radiotherapeutics for the treatment of cancer},

  author       = {Pryma, Daniel A. and Lieberman, Brian P. and Makvandi, Mehran and Mach, Robert H.},

  abstractNote = {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.},

  doi          = {},

  journal      = {},
number       = ,

  volume       = ,

  place        = {United States},

  year         = {2019},

  month        = {10}

}

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

Abstract

Citation Formats

Radiolabelled benzamide analogues, their synthesis and use in diagnostic imaging patent, February 2010

Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors patent, June 2008

Phenoxazine derivatives and methods of use thereof patent, May 2014

Isatin analogues and uses therefor patent, December 2012

Radiolabelled benzamide analogues, their synthesis and use in diagnostic imaging patent, May 2011

Therapeutic uses of bicyclic ligands of sigma 2 receptor patent, May 2012

1 H-[1, 2, 3] triazole substituted amino acids and uses thereof patent, May 2014

Pegylated fluorobenzamide analogues, their synthesis and use in diagnostic imaging patent, August 2013

Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors patent, November 2009

Modular platform for targeted therapeutic delivery patent, March 2012

Compounds, compositions, and methods for cancer imaging and therapy patent, July 1999

Compounds comprising 4-benzoylpiperidine as a sigma-1-selective ligand patent, February 2014

Detection of cancer cells in vitro using sigma-2 receptor ligands as radiotracers patent, February 2011

Radiolabelled fluorobenzamide analogues, their synthesis and use in diagnostic imaging patent, June 2012

Sigma 2 receptor ligands and therapeutic uses therefor patent, November 2009

Radiolabelled benzamide analogues, their synthesis and use in diagnostic imaging
patent, February 2010

Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors
patent, June 2008

Phenoxazine derivatives and methods of use thereof
patent, May 2014

Isatin analogues and uses therefor
patent, December 2012

Radiolabelled benzamide analogues, their synthesis and use in diagnostic imaging
patent, May 2011

Therapeutic uses of bicyclic ligands of sigma 2 receptor
patent, May 2012

1 H-[1, 2, 3] triazole substituted amino acids and uses thereof
patent, May 2014

Pegylated fluorobenzamide analogues, their synthesis and use in diagnostic imaging
patent, August 2013

Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors
patent, November 2009

Modular platform for targeted therapeutic delivery
patent, March 2012

Compounds, compositions, and methods for cancer imaging and therapy
patent, July 1999

Compounds comprising 4-benzoylpiperidine as a sigma-1-selective ligand
patent, February 2014

Detection of cancer cells in vitro using sigma-2 receptor ligands as radiotracers
patent, February 2011

Radiolabelled fluorobenzamide analogues, their synthesis and use in diagnostic imaging
patent, June 2012

Sigma 2 receptor ligands and therapeutic uses therefor
patent, November 2009