Method of high-pressure purification of [f-18]FEONM

Patent metadata

Field	Value
Publication number	US-11247947-B2
Application number	US-202117140246-A
Country	US
Kind code	B2
Filing date	Jan 4, 2021
Priority date	Jan 30, 2019
Publication date	Feb 15, 2022
Grant date	Feb 15, 2022

Abstract

A method is provided to purify [F-18]FEONM under a high pressure. The synthesis processes of [F-18]FEONM are integrated. An isolation process of non-toxic radio-high performance liquid chromatography (radio-HPLC) is used to purify the crude product. The method integrates a convention [F-18]FDG synthesizer and a novel radio-HPLC system together in a heat chamber. After radiofluorinating the precursor, the reaction product is purified with an alumina solid-phase column in advance to obtain the crude product while fluorine-18 is removed. Then, diphenyl semipreparative HPLC column is used for a final purification. A non-toxic solvent is used for mobile-phase eluting to remove the unreacted precursor and the phase-transfer solvent. The radiofluorination has a reaction yield about 50 percent (%). The method has an uncorrected radiochemical yield of 10˜20%. Both of the radio-HPLC and the radio-thin layer chromatography (radio-TLC) have radiochemical purity higher than 95%.

First claim

What is claimed is:

1. A method of high-pressure purification of [F-18]FEONM comprising steps of:
(a) radioflourinating a precursor (TEONM) to produce a crude product of [F-18]FEONM;
(b) injecting the crude product of [F-18]FEONM with an injector and a semipreparative diphenyl column via semipreparative high pressure pumping unit to isolate and purify such that a mobile-phase is obtained with an ethanol solution and wherein said (TEONM) precursor is eluted under a flow speed of 1.6 milliliters per minute (ml/min) and wherein the operating pressure is up to 700 psig;
(c) filter sterilizing remaining crude product of [F-18]FEONM obtained after eluting said (TEONM) precursor to obtain a purified product of [F-18]FEONM.

2. The method according to claim 1 , wherein said radiofluorination has a reaction yield of higher than 50 percent (%).

3. The method according to claim 1 , wherein said ethanol solution is obtained through diluting ethanol from 95% to 20% by adding normal saline.

4. The method according to claim 1 , wherein, in step (c), a filtering cartridge is used to filter said product of purified [F-18]FEONM to remove impurities and mycoplasmas and wherein said purified [F-18]FEONM obtained after said filter sterilization is stored in a sterile glass vial.

5. The method according to claim 4 , wherein said filtering cartridge has a filtering size of 0.15˜0.25 micrometers (μm).

6. The method according to claim 1 , wherein said product of purified [F-18]FEONM has a radio-chemical yield of 10˜20% and a radio-chemical purity higher than 95%.

7. The method according to claim 1 , wherein, after said (TEONM) precursor is processed through said radiofluorination, an alumina solid-phase extraction column is used to remove F-18 from said crude product of [F-18]FEONM.

Assignees

• Iner Aec Executive Yuan

Inventors

• Tu Yean-Hung
• Huang Li-Yuan
• Chen Jenn-Tzong
• Luo Tsai-Yueh
• Farn Shiou-Shiow
• Lin Wuu-Jyh

Classifications

• B01J20/284

  based on alumina · CPC title

• C07B63/00 Primary

  Purification; Separation (separation of optically-active compounds C07B57/00); Stabilisation; Use of additives · CPC title

• C07C253/34

  Separation; Purification · CPC title

• C07B59/001

  Acyclic or carbocyclic compounds · CPC title

• C07C253/14

  by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups · CPC title