Contrast agents for myocardial perfusion imaging

• US 20050191238A1
• Filed: 02/10/2005
• Published: 09/01/2005
• Est. Priority Date: 02/13/2004
• Status: Active Grant

• Current Assignee: Lantheus Medical Imaging, Inc. (Lantheus Holdings, Inc.)
• Original Assignee: Lantheus Medical Imaging, Inc. (Lantheus Holdings, Inc.)
• Inventors: Casebier, David S., Robinson, Simon P., Radeke, Heike S., Azure, Michael T., Dischino, Douglas D., Purohit, Ajay
• Granted Patent: US 7,344,702 B2
• Time in Patent Office: Days
• US Class Current: 424/1.11
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0052 Small organic molecules oligomers, polymers, dendrimers A61K49/0054
• CPC Class Codes: A61K 49/10 Organic compounds
• CPC Class Codes: A61K 49/22 Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: A61K 51/0421 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 51/0453 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 51/0459 having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 237/16 Two oxygen atoms
• CPC Class Codes: C07D 239/88 Oxygen atoms

Abstract

The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.

Claims

1. A method of imaging myocardial perfusion comprising administering to a patient a contrast agent which comprises an imaging moiety and a compound selected from deguelin, pyridaben, pyridimifen, tebufenpyrad, fenazaquin, a deguelin analog, a pyridaben analog, a pyridimifen analog, a tebufenpyrad analog, and an fenazaquin analog;

and scanning the patient using diagnostic imaging.

2. The method of claim 1, wherein the imaging moiety is a radioisotope for nuclear medicine imaging, a paramagnetic species for use in MRI imaging, an echogenic entity for use in ultrasound imaging, a fluorescent entity for use in fluorescence imaging, or a light-active entity for use in optical imaging.

3. A contrast agent comprising an imaging moiety and a compound selected from deguelin, pyridaben, pyridimifen, tebufenpyrad, fenazaquin a deguelin analog, a pyridaben analog, a pyridimifen analog, a tebufenpyrad analog, and an fenazaquin analog.

4. The contrast agent of claim 3 wherein the imaging moiety is a radioisotope for nuclear medicine imaging, a paramagnetic species for use in MRI imaging, an echogenic entity for use in ultrasound imaging, a fluorescent entity for use in fluorescence imaging, or a light-active entity for use in optical imaging.

5. The contrast agent of claim 4 wherein the paramagnetic species for use in MRI imaging is Gd³⁺, Fe³⁺, In³⁺, or Mn²⁺.

6. The contrast agent of claim 4 wherein the echogenic entity for use in ultrasound imaging is a fluorocarbon encapsulated surfactant microsphere.

7. The contrast agent of claim 4 wherein the radioisotope for nuclear medicine imaging is ¹¹C, ¹³N, ¹⁸F, ¹²³I, ¹²⁵I, ^99mTc, ⁹⁵Tc, ¹¹¹In, ⁶²Cu, ⁶⁴Cu, ⁶⁷Ga, or ⁶⁸Ga.

8. The contrast agent of claim 3 wherein the imaging moiety is ¹⁸F.

9. The contrast agent of claim 3 wherein the imaging moiety is ^99mTc.

10. The contrast agent of claim 3 of formula (I)

11. The contrast agent of claim 10, wherein

A is O;

B and C are each independently CH₃ or CH₂¹⁸F;

D and E are each independently CH₃ or CH₂¹⁸F;

R⁵, R⁶, R⁹, and R¹⁰ are each independently hydrogen or ¹⁸F; and

R¹¹ and R¹² together form an oxo group.

12. The contrast agent of claim 3 wherein the contrast agent is selected from

13. The contrast agent of claim 3 of formula (II),

14. The contrast agent of claim 13, wherein R²⁹ is C₁-C₆ alkyl wherein the C₁-C₆ alkyl is tert-butyl.

15. The contrast agent of claim 13, wherein R²⁸ is C₁-C₆ alkyl wherein the C₁-C₆ alkyl is methyl.

16. The contrast agent of claim 3 of formula (III)

17. The contrast agent of claim 16, wherein J is O and R²⁹ is C₁-C₆ alkyl wherein the C₁-C₆ alkyl is tert-butyl.

18. The contrast agent of claim 3 wherein the contrast agent is selected from

19. The contrast agent of claim 3 of formula (IV):

20. The contrast agent of claim 19, wherein J is C(═

O)N(H), and R²¹ is C₁-C₆ alkyl wherein the C₁-C₆ alkyl is methyl.

21. The contrast agent of claim 3 wherein the contrast agent is selected from

22. The contrast agent of claim 3 of formula (V)

23. The contrast agent of claim 22 wherein J is O.

24. The contrast agent of claim 22 of formula (VI)

25. The contrast agent of claim 3 wherein the contrast agent is selected from