公开(公告)号：US20230398239A1

公开(公告)日：2023-12-14

申请号：US18182850

申请日：2023-03-13

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul Sondel ,  Ravi Patel ,  Zachary Morris ,  Peter Carlson ,  Reinier Hernandez ,  Joseph Grudzinski

IPC: A61K51/04 ,  A61P35/00 ,  A61K41/00 ,  A61K51/10 ,  A61K39/395 ,  A61P35/04 ,  A61K38/20 ,  C07K16/30 ,  C07K14/52 ,  A61P37/04 ,  C07K16/28 ,  A61N5/00 ,  A61N5/10

CPC classification number: A61K51/0485 ,  A61P35/00 ,  A61K41/0038 ,  A61K51/1045 ,  A61K39/39558 ,  A61P35/04 ,  A61K51/0489 ,  A61K38/2013 ,  A61K51/0408 ,  C07K16/3084 ,  C07K14/52 ,  A61P37/04 ,  C07K16/2818 ,  A61K51/0497 ,  A61K39/39541 ,  A61N5/00 ,  A61N5/1001 ,  A61K9/0019

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 ether metal chelate, a radiohalogenated phospholipid ether, or other targeted radiotherapy (TRT) agent that is differentially retained within malignant solid tumor tissue, and either (a) 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 (b) performing immunotherapy in the subject by systemically administering to the subject an immunostimulatory agent, such as an immune checkpoint inhibitor. In a non-limiting example, the radioactive phospholipid ether metal chelate or radiohalogenated phospholipid ether 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, or wherein R1 comprises a radioactive halogen isotope. 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：US11633506B2

公开(公告)日：2023-04-25

申请号：US15809427

申请日：2017-11-10

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul Sondel ,  Ravi Patel ,  Zachary Morris ,  Peter Carlson ,  Reinier Hernandez ,  Joseph Grudzinski

IPC: A61K51/04 ,  A61P35/00 ,  A61K41/00 ,  A61K51/10 ,  A61K39/395 ,  A61P35/04 ,  A61K38/20 ,  C07K16/30 ,  C07K14/52 ,  A61P37/04 ,  C07K16/28 ,  A61N5/00 ,  A61N5/10 ,  A61K9/00 ,  A61K39/00

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 ether metal chelate, a radiohalogenated phospholipid ether, or other targeted radiotherapy (TRT) agent that is differentially retained within malignant solid tumor tissue, and either (a) 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 (b) performing immunotherapy in the subject by systemically administering to the subject an immunostimulatory agent, such as an immune checkpoint inhibitor. In a non-limiting example, the radioactive phospholipid ether metal chelate or radiohalogenated phospholipid ether 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, or wherein R1 comprises a radioactive halogen isotope. 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：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：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：US20180271470A1

公开(公告)日：2018-09-27

申请号：US15928812

申请日：2018-03-22

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weibo Cai ,  Robert Nickles ,  Reinier Hernandez ,  Stephen Graves

IPC: A61B6/00 ,  A61K51/00 ,  A61K31/4422 ,  A61K31/18 ,  A61B6/03 ,  A61B5/00 ,  G06T7/00

CPC classification number: A61B6/5217 ,  A61B5/425 ,  A61B6/037 ,  A61B6/4057 ,  A61K31/18 ,  A61K31/4422 ,  A61K51/00 ,  A61K51/121 ,  G01R33/481 ,  G06T7/0014 ,  G06T2207/10104 ,  G06T2207/30092

Abstract: Methods for imaging beta cells in pancreatic tissue using radioisotopes of manganese, which may be referred to as radiomanganese, are described. Example radioisotopes of manganese include Mn-52g, Mn-52m, and Mn-51. As one example, radiomanganese can be used to image pancreatic beta cells, in which radiomanganese shows a preferential uptake. This provides for applications such as quantifying beta cell mass (e.g., functional beta cell mass), assessing transplant viability, and monitoring the efficacy of drug treatments. A pharmacological agent can be administered to modulate the uptake of divalent metals by the pancreatic beta cells, which can be correlated to a modulated uptake of radiomanganese to estimate pancreatic beta cell mass, function, or both.