Radiotracer compositions

Patent metadata

Field	Value
Publication number	US-9987382-B2
Application number	US-201514877107-A
Country	US
Kind code	B2
Filing date	Oct 7, 2015
Priority date	Dec 9, 2010
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

The present invention relates to improved radiotracer imaging agent compositions, which comprises 18 F-labelled biological targeting moieties, wherein impurities which affect imaging in vivo are identified and suppressed. Also provided are radiopharmaceuticals comprising said improved compositions, together with radiofluorinated aldehyde compositions useful in preparing said radiotracer compositions. The invention also includes methods of imaging and/or diagnosis using the radiopharmaceutical compositions described.

First claim

What is claimed is:

1. A composition which comprises a radioactive aldehyde of Formula (A) together with one or more non-radioactive aldehydes of Formula (B):

wherein X 1 is 18 F, —O(CH 2 ) q 18 F or —OCH 2 —CH(OH)—CH 2 18 F and q is 2, 3 or 4;
X 2 is —N + (CH 3 ) 3 , —N(CH 3 ) 2 , —OCH 3 , H, —CH 3 , —OH, —SCH 3 , —OC 6 H 4 CHO or 19 F; and wherein the total concentration of Formula (B) present in the composition is greater than 0 and less than 150 μg/mL.

2. The composition of claim 1 , wherein the total concentration of Formula (B) present in the composition is greater than 0 and less than 100 μg/mL.

3. The composition of claim 1 , wherein X 1 is 18 F and X 2 is —N + (CH 3 ) 3 , —N(CH 3 ) 2 or —OH or combinations thereof and the total concentration of Formula (B) present in the composition is greater than 0 and less than 0.83 μmol/mL.

4. The composition of claim 1 , wherein X 1 is 18 F and X 2 is —N + (CH 3 ) 3 , —N(CH 3 ) 2 or —OH or combinations thereof.

5. The composition of claim 1 , which is provided as a solution.

6. The composition of claim 5 , wherein the solution comprises the solvent ethanol, aqueous ethanol, acetonitrile, or aqueous acetonitrile.

7. A method of radiolabeling a biological targeting moiety (BTM) comprising the steps:
(i) providing a biological targeting moiety functionalized with an aminooxy or hydrazine group;
(ii) reacting the functionalized-biological targeting moiety from step (i) with the radioactive aldehyde composition of claim 1 , wherein the radioactive aldehyde of Formula (A) condenses with the aminooxy or hydrazine group, to give the radiolabelled biological targeting moiety.

8. The method of claim 7 , wherein the BTM is selected from the group of a single amino acid, a 3-100 mer peptide, an enzyme substrate, an enzyme antagonist, an enzyme agonist, an enzyme inhibitor, and a receptor-binding compound.

9. The method of claim 7 , wherein the BTM is an RGD peptide.

10. The method of claim 7 , wherein the BTM is a peptide having the formula:

11. A method of making the composition of claim 1 , the method comprising forming the radioactive aldehyde of Formula (A) from trimethylammonium benzaldehyde followed by purifying the formed radioactive aldehyde of Formula (A) with a mixed mode cation exchange solid phase extraction (MCX+SPE) cartridge, to obtain the composition of claim 1 .

12. The method of claim 11 , wherein X 1 is 18 F and X 2 is —N + (CH 3 ) 3 , —N(CH 3 ) 2 or —OH or combinations thereof.

13. A composition provided as a solution, the composition comprising a radioactive aldehyde of Formula (A) together with one or more non-radioactive aldehydes of Formula (B):

wherein where X 1 is 18 F and X 2 is —N + (CH 3 ) 3 , —N(CH 3 ) 2 or —OH or combinations thereof and wherein the total concentration of Formula (B) present in the composition is greater than 0 and less than 100 μg/mL.

14. The composition of claim 13 , wherein the total concentration of Formula (B) present in the composition is greater than 0 and less than 0.83 μmol/mL.

15. The composition of claim 13 , wherein the solution comprises a solvent that is selected from ethanol, aqueous ethanol, acetonitrile, and aqueous acetonitrile.

16. A method of making the composition of claim 13 , comprising
forming the radioactive aldehyde of Formula (A) from trimethylammonium benzaldehyde followed by purifying the formed radioactive aldehyde of Formula (A) with a mixed mode cation exchange solid phase extraction (MCX+SPE) cartridge, to obtain the composition of claim 13 .

17. The method of claim 16 , wherein the total concentration of Formula (B) present in the composition is greater than 0 and less than 0.83 μmol/mL.

18. A method of radiolabel a biological targeting moiety (BTM) comprising:
(i) providing a biological targeting moiety functionalized with an aminooxy or hydrazine group;
(ii) reacting the functionalized-biological targeting moiety from step (i) with the radioactive aldehyde composition of claim 13 , wherein the radioactive aldehyde of Formula (A) condenses with the aminooxy or hydrazine group, to give the radiolabelled biological targeting moiety, wherein the BTM is a peptide comprising the fragment:

19. The method of claim 18 , wherein the BTM is precursor 1 and the radiolabeled biological targeting moiety is compound 1

20. The method of claim 18 , wherein the method is carried out using an automated synthesizer apparatus.

Assignees

• Ge Healthcare Ltd

Inventors

• Engell Torgrim
• Grigg Julian
• Mantzilas Dimitrios

Classifications

• C07B59/008

  Peptides; Proteins · CPC title

• A61K51/0497

  conjugates with a carrier being an organic compounds · CPC title

• C07K1/13

  Labelling of peptides · CPC title

• A61K51/088 Primary

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title

• A61K51/082

  the peptide being a RGD-containing peptide · CPC title