Phospholipid ether analogs for imaging and targeted treatment of pediatric solid tumors

Patent metadata

Field	Value
Publication number	US-12491202-B2
Application number	US-202117480239-A
Country	US
Kind code	B2
Filing date	Sep 21, 2021
Priority date	Jul 13, 2016
Publication date	Dec 9, 2025
Grant date	Dec 9, 2025

Abstract

It is disclosed herein that that certain alkylphosphocholine analogs are preferentially taken up by malignant pediatric tumor cells. The alkylphophocholine analogs are compounds having the formula:

or salts thereof, wherein n is an integer from 12 to 24; and R 2 is —N + (CH 3 ) 3 . The compounds can be used to treat pediatric solid tumors or to detect pediatric solid tumors. In therapeutic treatment, R 1 includes a radioactive iodine isotope that locally delivers therapeutic dosages of radiation to the malignant pediatric tumor cells that preferentially take up the compound. In detection/imaging applications, R 1 includes a detection moiety, such as a fluorophore or a radioactive iodine isotope.

First claim

The invention claimed is:

1 . A method for treating a malignant pediatric solid tumor in a subject, comprising administering to the subject having the malignant pediatric solid tumor an effective amount of a compound having the formula:

or a salt thereof, wherein:
R1 comprises a radioactive iodine isotope;
n is an integer from 12 to 24; and
R2 is —N + (CH3)3;

whereby the malignant pediatric solid tumor is treated in the subject.

2 . The method of claim 1 , wherein the radioactive iodine isotope is selected from the group consisting of 123 I, 125 I and 131 I.

3 . The method of claim 1 , wherein n is 18, and the radioactive iodine isotope is 123 I, 125 I or 131 I (the compound is [ 123 I]-CLR1404, [ 125 I]-CLR1404 or [ 131 I]-CLR1404).

4 . The method of claim 1 , wherein the compound is administered by parenteral, intranasal, sublingual, rectal, or transdermal delivery.

5 . The method of claim 1 , wherein the malignant pediatric solid tumor that is treated is selected from the group consisting of neuroblastoma (NB), Ewings sarcoma (EWS), osteosarcoma (OS), retinoblastoma (RB) Wilms' tumor (WT), and pediatric brain tumors.

6 . A method for inhibiting the proliferation or growth of malignant pediatric solid tumor cells, comprising contacting one or more malignant pediatric solid tumor cells with an effective amount of a compound having the formula:

or a salt thereof, wherein:
R1 comprises a radioactive iodine isotope;
n is an integer from 12 to 24; and
R2 is —N + (CH3)3;
whereby growth or proliferation of the malignant pediatric solid tumor cells is inhibited.

7 . The method of claim 6 , wherein the radioactive iodine isotope is selected from the group consisting of 123 I, 125 I and 131 I.

8 . The method of claim 7 , wherein n is 18, and the radioactive iodine isotope is 123 I, 125 I or 131 I (the compound is [ 123 I]-CLR1404, [ 125 I]-CLR1404 or [ 131 I]-CLR1404).

9 . The method of claim 6 , wherein the malignant pediatric solid tumor cells are selected from the group consisting of neuroblastoma (NB) cells, Ewings sarcoma (EWS) cells, osteosarcoma (OS) cells, retinoblastoma (RB) cells, Wilms' tumor (WT) cells, and pediatric brain tumor cells.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Otto Mario
• Baiu Dana C
• Bednarz Bryan P
• Weichert Jamey Paul

Classifications

• G01N33/57557 Primary

  of other specific parts of the body, e.g. brain · CPC title

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• A61K31/6615

  Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid · CPC title

• A61K31/69

  Boron compounds · CPC title

• A61K33/18

  Iodine; Compounds thereof · CPC title