Long-lived gadolinium based tumor targeted imaging and therapy agents

Patent metadata

Field	Value
Publication number	US-11623007-B2
Application number	US-202017032132-A
Country	US
Kind code	B2
Filing date	Sep 25, 2020
Priority date	Nov 6, 2015
Publication date	Apr 11, 2023
Grant date	Apr 11, 2023

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 therof. 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.

First claim

The invention claimed is:

1. A compound having the formula:

or a salt thereof, wherein:
R 1 comprises a chelating agent that is chelated to one or more gadolinium (Gd) atoms;
a is 0 or 1;
n is an integer from 12 to 30;
m is 0 or 1;
Y is selected from the group consisting of —H, —OH, —COOH, —COOX, —OCOX, and —OX, wherein X is an alkyl or an arylalkyl;
R 2 is selected from the group consisting of —N + H 3 , —N + H 2 Z, —N + HZ 2 , and —N + Z 3 , wherein each Z is independently an alkyl or an aroalkyl; and
b is 1 or 2.

2. The compound of claim 1 , wherein the one or more gadolinium atoms are in the form of a Gd(III) ion.

3. The compound of claim 1 , wherein a is 1 (aliphatic aryl-alkyl chain).

4. The compound of claim 1 , wherein a is 0 (aliphatic alkyl chain).

5. The compound of claim 1 , wherein m is 1 (acylphospholipid series).

6. The compound of claim 5 , wherein n is an integer between 12 and 20.

7. The compound of claim 5 , wherein Y is —OCOX, —COOX or —OX.

8. The compound of claim 7 , wherein X is —CH 2 CH 3 or —CH 3 .

9. The compound of claim 1 , wherein m is 0 (alkylphospholipid series).

10. The compound of claim 1 , wherein b is 1.

11. The compound of claim 1 , wherein n is 18.

12. The compound of claim 1 , wherein R 2 is —N + Z 3 .

13. The compound of claim 12 , wherein each Z is independently —CH 2 CH 3 or —CH 3 .

14. The compound of claim 13 , wherein each Z is —CH 3 .

15. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

16. A method for detecting or imaging one or more cancer tumor cells in a biological sample, comprising:
(a) contacting the biological sample with a compound of claim 1 ; and
(b) identifying individual cells or regions within the biological sample that are emitting signals characteristic of gadolinium, whereby one or more cancer tumor cells are detected or imaged.

17. The method of claim 16 , wherein the step of identifying individual cells or regions within the biological sample that are emitting signals characteristic of gadolinium is performed by magnetic resonance imaging (MRI).

18. The method of claim 16 , wherein the biological sample is part or all of a subject.

19. A method of diagnosing cancer in a subject, comprising performing the method of claim 16 , wherein the biogical sample is obtained from, part of, or all of a subject, and whereby if cancer cells are detected or imaged, the subject is diagnosed with cancer.

20. A method of treating cancer in a subject, comprising performing the method of claim 16 , wherein the biogical sample is part of or all of a subject, and directing an external radiotherapy beam to the identified individual cells or regions within the subject.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Weichert Jamey
• Pinchuk Anatoly
• Tome Wolfgang Axel

Classifications

• G01N33/575

  for cancer · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61N5/1048

  Monitoring, verifying, controlling systems and methods · CPC title

• G01N33/58

  involving labelled substances (G01N33/53 takes precedence) · CPC title

• C07F9/091

  with hydroxyalkyl compounds with further substituents on alkyl · CPC title