Labeled compounds and calcium sensing receptor ligands for imaging and uses thereof

Patent metadata

Field	Value
Publication number	US-2025057994-A1
Application number	US-202218578434-A
Country	US
Kind code	A1
Filing date	Jul 11, 2022
Priority date	Jul 12, 2021
Publication date	Feb 20, 2025
Grant date	—

Abstract

The present invention relates to labeled compounds suitable for positron emission tomography (PET) imaging and/or fluorescence imaging such as near-infrared fluorescence imaging (NIRF). The invention further relates to the use of these compounds for carrying out PET scans. imaging calcium sensing receptor (CSR)-positive organs. excising parathyroid tissue. protecting parathyroid tissue during thyroid surgery, and treating disorder(s) of a CSR-positive tissue in a subject.

First claim

1 . A radioisotope-labeled calcium sensing receptor (CSR) ligand comprising an aromatic ring, wherein the radioisotope is directly linked to the aromatic ring at one or more positions of the ring.

2 . The radioisotope-labeled CSR ligand of claim 1 , wherein the radioisotope is 18 F and/or 11 C.

3 - 10 . (canceled)

11 . The radioisotope-labeled CSR ligand of claim 1 , comprising formula II:

wherein Ar is substituted aryl and Y is alkyl.

12 . (canceled)

13 . The radioisotope-labeled CSR ligand of claim 11 , comprising Formula III:

14 . The radioisotope-labeled CSR ligand of claim 1 , selected from the group consisting of:

15 . The radioisotope-labeled CSR ligand of claim 13 , comprising formula I ( 18 F-cinacalcet):

16 . The radioisotope-labeled CSR ligand of claim 1 , comprising a formula selected from the group consisting of:

17 . The radioisotope-labeled CSR ligand of claim 1 , comprising a formula selected from the group consisting of:

18 . The radioisotope-labeled CSR ligand of claim 1 , comprising formula XI (evocalcet):

wherein radioisotope is directly linked to the naphthalene at position 4.

19 . The radioisotope-labeled CSR ligand of claim 18 , selected from the group consisting of:

20 . The radioisotope-labeled CSR ligand of claim 1 , selected from the group consisting of:

21 . A radioisotope-labeled calcium sensing receptor (CSR) ligand comprising formula XX (etelcalcetide hydrochloride) directly linked to 18 F:

22 . A labeled calcium sensing receptor (CSR) ligand suitable for use as a positron emission tomography (PET), fluorescence imaging (e.g., NIRF) probe and/or optical probe, comprising an CSR binding portion.

23 - 27 . (canceled)

28 . A halogenated fluorophore comprising a radioisotope, capable of preferential uptake in thyroid and/or parathyroid tissue.

29 . (canceled)

30 . The halogenated fluorophore of claim 28 , comprising formula XXII
( 18 F-T700):

31 - 33 . (canceled)

34 . A positron emission tomography (PET) probe comprising the ligand or fluorophore of claim 1 .

35 . A fluorescence imaging probe (e.g., NIRF probe) comprising the ligand or fluorophore of claim 1 .

36 - 40 . (canceled)

41 . A method of carrying out a PET scan on a subject, comprising administering to the subject the ligand, fluorophore, probe, and/or composition of claim 1 .

42 . A method of imaging tissue comprising a calcium sensing receptor (CSR) in a subject, comprising administering to the subject the ligand, fluorophore, probe, and/or composition of claim 1 .

43 . A method of imaging thyroid and/or parathyroid tissue in a subject, comprising administering to the subject the ligand, fluorophore, probe, and/or composition of claim 1 .

44 . A method of simultaneously carrying out a PET scan and fluorescence imaging (e.g., NIRF imaging) on a subject, comprising administering to the subject the ligand, fluorophore, probe, and/or composition of claim 1 .

45 . A method of identifying parathyroid tissue in a subject, comprising carrying out a PET scan and/or fluorescence imaging (e.g., NIRF imaging) on the subject using the ligand, fluorophore, probe, or composition of claim 1 , wherein the PET scan and/or fluorescence imaging identifies presence of parathyroid tissue.

46 - 57 . (canceled)

58 . A method of removing abnormal (e.g., adenomatous, hyperplastic, malignant, and/or ectopic parathyroid) tissue in a subject, comprising:
(a) carrying out a PET scan and/or fluorescence imaging (e.g., NIRF imaging) on the subject using the ligand, fluorophore, probe, and/or composition of claim 1 , wherein the PET scan and/or fluorescence imaging identifies presence of parathyroid tissue; (b) identifying present parathyroid tissue that is abnormal (e.g., adenomatous, hyperplastic, malignant, and/or ectopic); and (C) surgically excising the identified abnormal (e.g., adenomatous, hyperplastic, malignant, and/or ectopic) parathyroid tissue, thereby removing the abnormal (e.g., adenomatous, hyperplastic, malignant, and/or ectopic) parathyroid tissue.

59 . (canceled)

60 . A method of guiding surgery for the removal of parathyroid tissue in a subject, comprising carrying out a PET scan and/or fluorescence imaging (e.g., NIRF imaging) on the subject using the ligand, fluorophore, probe, and/or composition of claim 1 , wherein the PET scan and/or fluorescence imaging identifies presence of parathyroid tissue.

61 - 64 . (canceled)

65 . A method of guiding surgery for the protection of parathyroid tissue during thyroid surgery in a subject, comprising carrying out a PET scan and/or fluorescence imaging (e.g., NIRF imaging) on the subject using the ligand, fluorophore, probe, and/or composition of claim 1 , wherein the PET scan and/or fluorescence imaging identifies presence of parathyroid tissue.

66 - 70 . (canceled)

71 . A method of determining target regions for surgical removal of parathyroid tissue of a subject with hyperparathyroidism or a subject at risk for or suspected to have or develop hyperparathyroidism, comprising
(a) carrying out a PET scan and/or fluorescence imaging (e.g., NIRF imaging) on the subject using the ligand, fluorophore, probe, and/or composition of claim 1 , wherein the PET scan and/or fluorescence imaging identifies presence of parathyroid tissue; and (b) identifying one or more regions(s) of the subject comprising the presence of adenomatous, hyperplastic, malignant, and/or ectopic parathyroid tissue, wherein the presence of parathyroid tissue in the one or more region(s) indicates the region(s) as a target region of the subject for surgical removal of parathyroid tissue.

72 - 76 . (canceled)

77 . A method of treating hyperparathyroidism in a subject, comprising determining the suitability of a subject with hyperparathyroidism or a subject at risk for or suspected to have or develop hyperparathyroidism to surgical removal of parathyroid tissue by carrying out a PET scan on the subject usi

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Li Zibo
• Kim Lawrence
• Wu Zhanhong

Classifications

• A61K2123/00

  Preparations for testing in vivo · CPC title

• A61K51/0402

  carboxylic acid carriers, fatty acids (amino acids A61K51/0406) · CPC title

• C07D209/08

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• C07D207/08

  with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms · CPC title

• C07C323/60

  with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms · CPC title