Tumor imaging agents, methods and kits

• US 6,187,286 B1
• Filed: 05/01/1997
• Issued: 02/13/2001
• Est. Priority Date: 12/27/1996
• Status: Expired due to Term

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Babich, John W., Elmaleh, David R.
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US08/846,999
• Time in Patent Office: 1,384 Days
• Field of Search: 424/9.1, 424/9.3, 424/9.4, 424/9.5, 424/9.6, 424/9.7, 424/1.11, 424/1.65, 424/1.73, 206/223, 206/569, 206/570, 536/27.6, 536/27.7, 536/26.26, 536/26.8, 536/26.72, 536/27.1, 536/26.1, 534/7, 534/10-16
• US Class Current: 424/1.73
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds

Abstract

The invention provides tumor imaging agents comprising a radionuclide in association with a nucleotide polyphosphate targeting molecule. Methods for using the tumor imaging agents and kits containing the tumor imaging agents or components suitable for production of the tumor imaging agents are also provided.

Claims

1. A tumor imaging agent comprising a radionuclide associated with a targeting moiety by way of an auxiliary molecule, said targeting moiety comprising a residue of nucleotide polyphosphate precursor having formula A), B), C), or D):

2. The agent of claim 1 further comprising a radionuclide selected from the group consisting of ¹²³I, ^99mTc, ¹⁸F, ⁶⁸Ga, ⁶²Cu, and ¹¹¹In.

3. The agent of claim 1, wherein said imaging agent comprises the product of combining said polyphosphate precursor with a chelating structure which chelates said radionuclide.

4. The agent of claim 3, wherein the chelating structure is selected from the group consisting of an —

N₂S₂ structure, an —

NS₃ structure, an —

N₄ structure, an isonitrile, a hydrazine, a HYNIC group-containing structure, 2-methylthiolnicotinic acid-group, and a carboxylate group-containing structure.

5. The agent of any of claims 3-4, wherein the radionuclide is ^99mTc.

8. A method of imaging tumors in a mammal which comprises the steps of administering to the mammal the imaging agent of claim 1, or claim 7, and imaging the mammal to obtain an image.

9. The method of claim 8 in which the method detects a tumor in a mammal, said method comprising the steps of administering to the mammal the imaging agent and detecting the spatial distribution of the agent accumulated in the mammal'"'"'s.

11. The method of claim 8 further comprising reacting the polyphosphate precursor with a radionuclide containing moiety.

6. A tumor imaging agent comprising a radionuclide associated with a targeting moiety by way of an auxiliary molecule, said targeting moiety comprising a residue of nucleotide polyphosphate precursor having formula A), B), C), or D):

10. A method of imaging tumors in a mammal which comprises the steps of administering to the mammal the imaging agent of claim 6 and imaging the mammal to obtain an image.

19. The agent of claim 6 which each of Nu₁—

Nu₄ is independently selected from the group nucleosides consisting of adenosine, guanosine, cytidine, thymidine, uridine, and inosine.

7. A tumor imaging agent comprising a complex of ^99mTc having the formula:

where Ad is adenosine, and p is PO₂H, and X is a ^99mTc-containing chelating moiety.

12. A kit for tumor imaging which comprises a supply of a targeting precursor, said targeting precursor having formula A), B), C), or D):

13. The kit of claim 12 further comprising a chelating agent, the chelating agent comprising:

a) an auxiliary molecule selected from the group consisting of mannitol, gluconate, glucoheptonate, and tartrate; and

b) a tin-containing reducing agent.

14. The kit of claim 12 further comprising a radionuclide selected from the group consisting of ¹²³I, ^99mTc, ¹⁸F, ⁶⁸Ga, ⁶²Cu, and ¹¹¹In.

15. The kit of claim 12, wherein said kit further comprises at least one chelating structure.

16. The kit of claim 15, wherein the chelating structure is selected from the group consisting of an —

N₂S₂ structure, an —

NS₃ structure, an —

N₄ structure, an isonitrile, a hydrazine, a HYNIC group-containing structure, 2-methylthiolnicotinic acid-group, and a carboxylate group-containing structure.

17. The kit of any of claims 15 or 16 wherein the radionuclide is ^99mTc.

18. A kit for tumor imaging which comprises a supply of a targeting precursor, said targeting precursor having formula A), B), C), or D):