Wisconsin Alumni Research Foundation

Reinier Hernandez

Anatoly Pinchuk

Jamey Paul Weichert

Paul M Sondel

Zachary Scott Morris

Peter Carlson

Joseph J Grudzinski

Ravi Bhasker Patel

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. Rincludes a chelating moiety; a is 0 or 1; n is an integer from 12 to 21; and Rincludes 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.

PSMA-targeting ligands with optimal properties for imaging and therapy

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 Rcomprises 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 Rcomprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and Ris &#x2014;N(CH).

Using targeted radiotherapy (TRT) to drive anti-tumor immune response to immunotherapies

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: Rincludes 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 &#x2014;H, &#x2014;OH, &#x2014;COOH, &#x2014;COOX, &#x2014;OCOX, or &#x2014;OX, wherein X is an alkyl or an arylalkyl; Ris &#x2014;NH, &#x2014;NHZ, &#x2014;NHZ, or &#x2014;NZ, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2.

Radioactive phospholipid metal chelates for cancer imaging and therapy

Growing community of inventors

Madison, WI, United States of America

Reinier Hernandez