公开(公告)号：US20200330567A1

公开(公告)日：2020-10-22

申请号：US16919191

申请日：2020-07-02

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul M. Sondel ,  Anatoly Pinchuk ,  Zachary Morris ,  Mario Otto ,  Bryan Bednarz

IPC: A61K39/00 ,  A61K39/395 ,  A61K39/39 ,  A61K51/04

Abstract: A method of treating a malignant solid tumor in a subject is disclosed herein. The method includes the steps of administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by intratumorally injecting into (or treating via a separate method) at least one of the malignant solid tumors a composition that includes one or more agents capable of stimulating specific immune cells within the tumor microenvironment. In certain exemplary embodiments, the radiohalogenated compound has the formula: wherein R1 is a radioactive halogen isotope, n is 18 and R2 is —N+(CH3)3.

公开(公告)号：US20250082797A1

公开(公告)日：2025-03-13

申请号：US18829184

申请日：2024-09-09

Applicant: Wisconsin Alumni Research Foundation

Inventor： Reinier Hernandez ,  Anatoly Pinchuk ,  Liudmila Lambert Lepesevich ,  Zachary Rosenkrans ,  Anna Thickens ,  Nathan Clemons

IPC: A61K51/12 ,  A61K51/04

Abstract: Methods of radiolabeling of cell surface glycans for in vivo cell tracking and imaging as well as populations of radiolabeled cells and uses thereof are disclosed.

公开(公告)号：US12156921B2

公开(公告)日：2024-12-03

申请号：US18303708

申请日：2023-04-20

Applicant: Wisconsin Alumni Research Foundation

Inventor： Reinier Hernandez ,  Anatoly Pinchuk

IPC: A61K51/04 ,  A61P13/08 ,  A61P35/00

Abstract: Theranostic agents incorporating a chelating moiety that can chelate a radioactive metal isotope and a PSMA-targeting moiety are disclosed herein. The theranostic agents, which can be used to treat and/or detect cancers associated with increased PSMA expression, have the formula: and include complexes, anions or salts thereof. R1 includes a chelating moiety; a is 0 or 1; n is an integer from 12 to 21; and R2 includes a prostate specific membrane antigen (PSMA)-targeting moiety. Optionally, the chelating moiety is chelated to a metal atom, where the metal atom is a positron or single photon emitting metal isotope, or an alpha, beta, or Auger emitting metal isotope.

公开(公告)号：US20200291049A1

公开(公告)日：2020-09-17

申请号：US16891181

申请日：2020-06-03

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Anatoly Pinchuk ,  Reinier Hernandez

IPC: C07F9/6524 ,  C07B59/00 ,  G01N33/574 ,  A61K51/04 ,  A61N5/10 ,  G01N33/60

Abstract: Alkylphosphocholine analogs incorporating a chelating moiety that chelates a radioactive metal isotope are disclosed herein. The alkylphophocholine analogs, which can be used to treat or detect solid tumors, have the formula: R1 includes a chelating agent that is chelated to a metal atom, wherein the metal atom is a positron or single photon emitting metal isotope with a half life of greater than or equal to 4 hours, or an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R2 is —N+H3, —N+H2Z, —N+HZ2, or —N+Z3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2.

公开(公告)号：US10751430B2

公开(公告)日：2020-08-25

申请号：US15658535

申请日：2017-07-25

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul Sondel ,  Anatoly Pinchuk ,  Zachary Morris ,  Mario Otto ,  Bryan Bednarz ,  Peter Carlson

IPC: A61K51/04 ,  A61K39/395 ,  A61K38/20 ,  C07K16/30 ,  A61K39/00 ,  A61K9/00

Abstract: The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid metal chelate compound that is differentially retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or by performing another method of in situ tumor vaccination. In a non-limiting example, the radioactive phospholipid metal chelate compound has the formula: wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is —N+(CH3)3.

公开(公告)号：US20200237935A1

公开(公告)日：2020-07-30

申请号：US16851585

申请日：2020-04-17

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Reinier Hernandez ,  Ray Zhang ,  Anatoly Pinchuk

IPC: A61K51/04 ,  A61K9/00 ,  A61B5/055 ,  C07B59/00 ,  A61K49/00 ,  C07F9/6524 ,  A61K49/10 ,  A61K49/08

Abstract: Dual-modality contrast agents are disclosed herein, having the general formula: R1 includes a chelating moiety that is chelated to a Mn2+ isotope. The disclosed contrast agents differentially target a wide range of malignant tumor tissues, and can be simultaneously used as contrast agents for both magnetic resonance imaging (MRI) and positron emission topography (PET) imaging. Accordingly, the disclosed contrast agent can be used in diagnosing and monitoring solid tumor cancers.

公开(公告)号：US20190184014A1

公开(公告)日：2019-06-20

申请号：US16285358

申请日：2019-02-26

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Anatoly Pinchuk ,  Wolfgang Axel Tome

IPC: A61K41/00 ,  A61N5/10 ,  A61K49/08 ,  A61K49/10 ,  C07F9/11 ,  C07F9/09 ,  C07F9/6561 ,  C07F9/6524 ,  C07F9/6515 ,  G01N33/60 ,  A61K51/04 ,  C07F9/10 ,  G01N33/58 ,  G01N33/574

Abstract: Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: or a salt thereof. R1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R2 is —N+H3, —N+H2Z, —N+HZ2, or —N+Z3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

公开(公告)号：US10265398B2

公开(公告)日：2019-04-23

申请号：US15343580

申请日：2016-11-04

Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATION

Inventor： Jamey Weichert ,  Anatoly Pinchuk ,  Wolfgang Axel Tomé

IPC: A61K49/00 ,  A61K51/04 ,  G01N33/58 ,  C07F9/10 ,  A61K41/00 ,  A61K49/08 ,  A61K49/10 ,  G01N33/574 ,  A61N5/10 ,  G01N33/60 ,  C07F9/6515 ,  C07F9/6524 ,  C07F9/6561 ,  C07F9/09 ,  C07F9/11 ,  A61K39/00

Abstract: Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: or a salt thereof. R1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R2 is —N+H3, —N+H2Z, —N+HZ2, or —N+Z3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

公开(公告)号：US12109256B2

公开(公告)日：2024-10-08

申请号：US16919191

申请日：2020-07-02

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul M. Sondel ,  Anatoly Pinchuk ,  Zachary Morris ,  Mario Otto ,  Bryan Bednarz

IPC: A61K39/00 ,  A61K39/39 ,  A61K39/395 ,  A61K51/04

CPC classification number: A61K39/001 ,  A61K39/0011 ,  A61K39/39 ,  A61K39/39558 ,  A61K51/0408 ,  A61K51/041 ,  A61K51/0489 ,  A61K2039/505 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/55511 ,  A61K2039/55533 ,  A61K2039/572 ,  A61K2039/58 ,  A61K2039/585

Abstract: A method of treating a malignant solid tumor in a subject is disclosed herein. The method includes the steps of administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by intratumorally injecting into (or treating via a separate method) at least one of the malignant solid tumors a composition that includes one or more agents capable of stimulating specific immune cells within the tumor microenvironment. In certain exemplary embodiments, the radiohalogenated compound has the formula:




wherein R1 is a radioactive halogen isotope, n is 18 and R2 is —N+(CH3)3.

公开(公告)号：US10813998B2

公开(公告)日：2020-10-27

申请号：US16285358

申请日：2019-02-26

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Anatoly Pinchuk ,  Wolfgang Axel Tome

IPC: A61K41/00 ,  A61K49/10 ,  A61K51/04 ,  A61K49/08 ,  G01N33/574 ,  G01N33/58 ,  C07F9/6515 ,  C07F9/6524 ,  C07F9/6561 ,  C07F9/09 ,  C07F9/11 ,  A61N5/10 ,  C07F9/10 ,  G01N33/60 ,  A61K39/00

Abstract: Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: or a salt thereof. R1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R2 is —N+H3, —N+H2Z, —N+HZ2, or —N+Z3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.