Calixarene conjugates useful as MRI and CT diagnostic imaging agents

• US 5,622,687 A
• Filed: 11/15/1994
• Issued: 04/22/1997
• Est. Priority Date: 11/15/1994
• Status: Expired due to Fees

• Current Assignee: Molecular Biosystems, Inc (Alliance Pharmaceutical Corporation)
• Original Assignee: Molecular Biosystems, Inc (Alliance Pharmaceutical Corporation)
• Inventors: Krishnan, Ashwin M., Lohrmann, Rolf
• Primary Examiner(s): Hollinden, Gary E.
• Application Number:
  US08/340,206
• Time in Patent Office: 889 Days
• Field of Search: 424/9.33, 424/9.36, 424/9.364, 424/9.37, 514/492, 514/502, 514/836, 436/173, 128/653.4, 128/654
• US Class Current: 424/9.33
• CPC Class Codes: A61K 49/0442 Polymeric X-ray contrast-enhancing agent comprising a halogenated group
• CPC Class Codes: A61K 49/126 Linear polymers, e.g. dextran, inulin, PEG
• CPC Class Codes: A61K 49/128 comprising multiple complex or complex-forming groups, being either part of the linear polymeric backbone or being pending groups covalently linked to the linear polymeric backbone
• CPC Class Codes: A61K 49/20 containing free radicals , e.g. trityl radical for overhauser
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Calixarene conjugates useful for imaging, particularly magnetic resonance imaging (MRI) and computed tomography (CT) are described. Said calixarene conjugates comprise (i) a calixarene backbone, and (ii) at least one imaging moiety linked thereto, and may be of the formula: ##STR1## wherein at least one of the R¹ and R⁴ substituents comprises an imaging moiety, the remaining R¹ and R⁴ substituents are spectator groups, J is an ortho-linker, and n is an integer from 4 to 8. Imaging moieties useful for CT imaging include those comprising two or more iodine atoms. Imaging moieties useful for MRI include (i) organic moieties comprising four or more fluorine atoms; (ii) nitroxyl spin labeled moieties; and (iii) metal chelate moieties.

Claims

1. A calixarene conjugate comprising:

(a) a calixarene backbone; and

(b) at least one MAGNETIC RESONANCE imaging moiety linked thereto.

2. The calixarene conjugate of claim 1 wherein the conjugate has at least two imaging moieties, wherein at least one moiety is a CT imaging moiety and at least one moiety is a MR imaging moiety.

3. A calixarene conjugate of the formula:

##STR10## wherein at least one of the R¹ and R⁴ substituents comprises A MAGNETIC RESONANCE imaging moiety, the remaining R¹ and R⁴ substituents, if any, are spectator groups, J is an ortho-linker, and n is an integer from 4 to 8.

4. The calixarene conjugate of claim 3, wherein said ortho-linker is --CH₂ --.

5. The calixarene conjugate of claim 3, wherein n=4.

6. The calixarene conjugate of claim 3, wherein all the R¹ groups comprise a magnetic resonance imaging moiety.

7. The calixarene conjugate of claim 3, wherein all the R⁴ groups comprise A MAGNETIC RESONANCE imaging moiety.

8. The calixarene conjugate of claim 3, wherein said MR imaging moiety comprises four or more fluorine atoms.

9. The calixarene conjugate of claim 8, wherein said fluorine atoms are present as part of --CF₃ groups.

10. The calixarene conjugate of claim 9, wherein said fluorine atoms are present as part of one or more --C(CF₃)₃ groups.

11. The calixarene conjugate of claim 3, wherein said MR imaging moiety comprises at least one nitroxyl spin labeled moiety.

12. The calixarene conjugate of claim 11, wherein said nitroxyl spin labeled moiety comprises a piperidinoxyl moiety.

13. The calixarene conjugate of claim 3, wherein said MR imaging moiety comprises at least one metal chelate moiety.

14. The calixarene conjugate of claim 13, where said metal chelate moiety comprises a DTPA moiety.

15. The calixarene conjugate of claim 13, where said metal chelate moiety comprises a Gd(III) ion.

16. An imaging agent formulation comprising:

(a) a calixarene conjugate comprising;

a calixarene backbone, and

at least one MR imaging moiety linked thereto; and

(b) a pharmaceutically acceptable carrier.

17. A method of MRI comprising:

(a) administering an effective amount of a calixarene conjugate having at least one MR imaging moiety to a patient; and

(b) acquiring an MR image of at least a portion of the patient while the calixarene conjugate is present in the patient.