Imaging agents and methods of use

Patent metadata

Field	Value
Publication number	US-10953113-B2
Application number	US-201716465887-A
Country	US
Kind code	B2
Filing date	Nov 30, 2017
Priority date	Dec 2, 2016
Publication date	Mar 23, 2021
Grant date	Mar 23, 2021

Abstract

An imaging agent and a method of its use for imaging a necrosis in a tissue of a subject. The imaging method may be positron emission tomography (PET). In at least one embodiment the imaging agent comprises 2-deoxy-2-[18F]fluoroglucaric acid (18F-FGA), or a pharmaceutically-acceptable salt thereof. The imaging agent may be disposed in a pharmaceutically-acceptable excipient, carrier, diluent, or vehicle. The imaging agent may be contained within a kit. The disclosure includes in at least one embodiment a method of preparing a radiopharmaceutical such as 18F-FGA for use in imaging.

First claim

What is claimed is:

1. A process for preparing a radiopharmaceutical composition, comprising:
combining a quantity of 2-deoxy-2-[ 18 F]fluoro-D-glucose ( 18 F-FDG) with an oxidizing agent, a reaction accelerator, and an alkaline buffering agent to form a first mixture;
adding a reaction initiator to the first mixture to form a reaction mixture; and
incubating the reaction mixture, wherein substantially all of the 18 F-FDG is converted into 2-deoxy-2-[ 18 F]fluoroglucaric acid ( 18 F-FGA) in less than about 10 minutes after adding the reaction initiator, and wherein the conversion of 18 F-FDG into 18 F-FGA occurs without monitoring and adjusting the pH of the reaction mixture, thereby preparing the radiopharmaceutical composition and, after conversion of the 18 F-FDG into 18 F-FGA, adding an acid to the reaction mixture to change the pH of the reaction mixture to a pH in a range of about 6.5 to about 7.5.

2. The process of claim 1 , wherein the oxidizing agent is selected from the group consisting of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), 4-hydroxy-TEMPO, TEMPO methacrylate, 4-oxo-TEMPO, 4-amino-TEMPO, 4-acetamido-TEMPO, 4-carboxy-TEMPO, 4-hydroxy-TEMPO benzoate, 4-(2-iodoacetamido)-TEMPO, 4-maleimido-TEMPO, 4-isothiocyanato-TEMPO, 4-(2-bromoacetamido)-TEMPO, 4-methoxy-TEMPO, 4-cyano-TEMPO, 4-amino-4-carboxy-TEMPO, 4-phosphonooxy-TEMPO hydrate, 2,2,6,6-tetramethyl-4-(methylsulfonyloxy)-1-piperidinooxy, hydrogen peroxide, sodium hypochlorite, calcium hypochlorite, ozone, nitric acid, permanganate compounds, halogens, metal-catalyzed oxidation agents, gold nanoparticles, nanoparticles which mimic peroxidase activity-mimicking nanoparticles, glucose oxidase, and glucose-oxidizing enzymes or compounds.

3. The process of claim 1 , wherein the alkaline buffering agent has a buffering capacity in a pH range of about 9 to about 12.

4. The process of claim 1 , wherein the incubating step occurs at a reaction temperature in a range of about 0° C. to about 25° C.

5. The process of claim 1 , wherein the oxidizing agent is a free compound, or is linked to a bead, resin, or polymer.

6. The process of claim 1 , wherein the reaction initiator is selected from the group consisting of sodium hypochlorite and calcium hypochlorite and the reaction accelerator is selected from the group consisting of sodium bromide and potassium bromide.

7. The process of claim 1 , wherein the alkaline buffering agent is a bicarbonate buffer.

8. The process of claim 7 , wherein the bicarbonate buffer is sodium bicarbonate.

Assignees

• Univ Oklahoma

Inventors

• Awasthi Vibhudutta
• Houson Hailey
• Nkepang Gregory

Classifications

• C07C59/295

  containing halogen · CPC title

• C07B59/005

  Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids · CPC title

• A61K51/0491 Primary

  Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07C51/29

  with halogen-containing compounds which may be formed in situ · CPC title