Alkylphosphocholine analogs for multiple myeloma imaging and therapy

Patent metadata

Field	Value
Publication number	US-2016296646-A1
Application number	US-201615095641-A
Country	US
Kind code	A1
Filing date	Apr 11, 2016
Priority date	Apr 10, 2015
Publication date	Oct 13, 2016
Grant date	—

Abstract

It is disclosed herein that that certain alkylphosphocholine analogs are preferentially taken up by multiple myeloma 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 + H 3 , —N + H 2 X, —N + HX 2 , or —N + HX 3 , wherein each X is independently —CH 3 or —C 2 H 5 . The compounds can be used to treat multiple myeloma or to detect multiple myeloma. In therapeutic treatment, R 1 includes a radionuclide that locally delivers therapeutic dosages of radiation to the multiple myeloma tumors cells that preferentially take up the compound. In detection/imaging applications, R 1 includes a detection moiety, such as a fluorophore or a radiolabel.

First claim

1 .- 52 . (canceled)

53 . A method for treating multiple myeloma in a subject, comprising administering to a subject having multiple myeloma an effective amount of a compound having the formula:

or a salt thereof, wherein:
R 1 is a radioactive iodine isotope;
n is an integer from 12 to 24; and
R 2 is —N + (CH 3 ) 3 ;
whereby multiple myeloma is treated in the subject.

54 . The method of claim 53 , wherein the radioactive iodine isotope is selected from the group consisting of 124 I, 125 I and 131 I.

55 . The method of claim 54 , wherein the radioactive iodine isotope is 125 I or 131 I.

56 . The method of claim 55 , wherein the radioactive iodine isotope is 131 I.

57 . The method of claim 53 , wherein n is 18.

58 . The method of claim 57 , wherein the radioactive iodine isotope is 131 I (the compound is [ 131 I]-CLR1404).

59 . The method of claim 53 , wherein the compound is administered by parentaeral, intranasal, sublingual, rectal, or transdermal delivery.

60 . A method for inhibiting the proliferation or growth of multiple myeloma tumor cells, comprising contacting one or more multiple myeloma tumor cells with an effective amount of a compound having the formula:

or a salt thereof, wherein:
R 1 is a radioactive iodine isotope;
n is an integer from 12 to 24; and
R 2 is —N + (CH 3 ) 3 ;
whereby growth or proliferation the multiple myeloma tumor cells is inhibited.

61 . The method of claim 60 , wherein the radioactive iodine isotope is selected from the group consisting of 124 I, 125 I and 131 I.

62 . The method of claim 61 , wherein the radioactive iodine isotope is 125 I or 131 I.

63 . The method of claim 62 , wherein the radioactive iodine isotope is 131 I.

64 . The method of claim 60 , wherein n is 18.

65 . The method of claim 64 , wherein the radioactive iodine isotope is 131 I (the compound is [ 131 I]-CLR1404).

66 . The method of claim 60 , wherein the method is performed in vivo, ex vivo, or in vitro.

67 . A method for detecting or imaging one or more multiple myeloma tumor cells in a biological sample, comprising:
(a) contacting the biological sample with a compound having the formula:

or a salt thereof, wherein:
R 1 comprises a radioactive iodine isotope or a fluorophore;
n is an integer from 12 to 24; and
R 2 is —N + (CH 3 ) 3 , whereby the compound is differentially taken up by multiple myeloma tumor cells within the biological sample; and
(b) identifying individual cells or regions within the biological sample that are emitting signals characteristic of the radioactive iodine isotope or fluorophore, whereby one or more multiple myeloma tumor cells are detected or imaged.

68 . The method of claim 67 , wherein R 1 is a fluorophore, and wherein the signals characteristic of the fluorophore comprise optical signals.

69 . The method of claim 68 , wherein the compound is CLR1501 or CLR1502.

70 . The method of claim 67 , wherein the radioactive iodine isotope is selected from the group consisting of 123 I, 124 I, 125 I, and 131 I.

71 . The method of claim 70 , wherein the compound is [ 124 I]-CLR1404.

72 . A method of diagnosing multiple myeloma in a subject, comprising performing the method of claim 67 , wherein the biological sample is obtained from, part of, or all of a subject, and whereby if myeloma tumor cells are detected or imaged, the subject is diagnosed with multiple myeloma.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Weichert Jamey Paul
• Pak Chorom
• Titz Benjamin
• Asimakopoulos Fotis
• Marino Roberta
• Otto Mario
• Kozak Kevin R

Classifications

• G01N33/57557

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

• G01N33/582

  with fluorescent label · CPC title

• G01N33/60

  involving radioactive labelled substances · CPC title

• A61K51/0489 Primary

  Phosphates or phosphonates, e.g. bone-seeking phosphonates; (phospholipids: A61K51/0408; nucleotides or nucleic acids: A61K51/0491) · CPC title

• G01N33/57407

  Physics · mapped topic