Apparatus and method for synthesizing F-18 labeled radioactive pharmaceuticals

Patent metadata

Field	Value
Publication number	US-9254471-B2
Application number	US-201214117622-A
Country	US
Kind code	B2
Filing date	May 11, 2012
Priority date	May 13, 2011
Publication date	Feb 9, 2016
Grant date	Feb 9, 2016

Abstract

Method and apparatus for synthesizing an F-18 labeled radioactive pharmaceutical by labeling a precursor with an F-18 radioactive isotope, by reacting the labeled precursor to obtain a labeled pharmaceutical, by separating impurities from the labeled pharmaceutical to provide a purified labeled pharmaceutical, and by collecting the purified labeled pharmaceutical. The apparatus includes a labeling cartridge that contains the precursor, receives the isotope, and causes a labeling reaction to provide the labeled precursor; a synthesizing container that receives the labeled precursor, receives at least one reagent effective to hydrolyze the labeled precursor, and within which the labeled precursor undergoes a hydrolysis reaction to provide the labeled pharmaceutical; and a separation cartridge that receives the labeled pharmaceutical, and contains a polymer compound that separates impurities into polar compounds and nonpolar compounds to provide the purified labeled pharmaceutical. The labeling and separation cartridges may be contained in a removable cassette.

First claim

The invention claimed is:

1. An apparatus for synthesizing an F-18 labeled radioactive pharmaceutical by labeling a precursor of a pharmaceutical with an F-18 radioactive isotope to provide an F-18 labeled precursor, by reacting the F-18 labeled precursor to obtain a crude F-18 labeled pharmaceutical, by separating impurities from the crude F-18 labeled pharmaceutical to provide a purified F-18 labeled pharmaceutical, and by collecting the purified F-18 labeled pharmaceutical, the apparatus comprising:
an F-18 radioactive isotope supplier which supplies an F-18 radioactive isotope;
a reagent supplier which supplies at least one reagent;
a labeling cartridge that contains the precursor, that receives the F-18 radioactive isotope, and that causes a labeling reaction to provide the F-18 labeled precursor;
a first heating unit that selectively heats the labeling cartridge;
a synthesizing container that receives the F-18 precursor, that receives at least one reagent effective to hydrolyze the F-18 labeled precursor, and within which the F-18 labeled precursor undergoes a hydrolysis reaction to provide the F-18 labeled pharmaceutical;
a second heating unit which selectively heats the synthesizing container;
a separation cartridge that receives the F-18 labeled pharmaceutical, and that contains a polymer compound that separates impurities into polar compounds and nonpolar compounds to provide a purified F-18 labeled pharmaceutical;
a waste liquid container which receives and contains fluid which is discarded after synthesis;
a collecting container which collects the F-18 labeled pharmaceutical from the separation cartridge;
a transmitting gas supplier which supplies a flow of transmitting gas;
a cleansing liquid supplier which supplies a cleansing liquid;
a connection tube which connects the F-18 radioactive isotope supplier, the reagent supplier, the labeling cartridge, the separation cartridge, the synthesizing container, the waste liquid container, the collection container, the transmitting gas supplier, and the cleansing liquid supplier together;
a plurality of control valves which are disposed at predetermined positions of the connection tube to perform selective opening and closing operations; and
a controller which controls operations of the first heating unit, the second heating unit, and the plurality of the control valves.

2. The apparatus of claim 1 , wherein the reagent supplier comprises:
a first organic solvent supplying unit which supplies a first organic solvent for removing water from within the labeling cartridge;
a second organic solvent supplying unit which supplies a second organic solvent which is an organic solvent containing acid or a mixed liquid of water and organic solvent for use as said at least one reagent effective to hydrolyze the F-18 labeled precursor;
an alkaline aqueous solution supplying unit which supplies an alkaline aqueous solution for neutralizing synthesized liquid within the synthesizing container; and
a third organic solvent supplying unit which supplies a third organic solvent for elution of the F-18 labeled pharmaceutical within the separation cartridge.

3. The apparatus of claim 1 , wherein the precursor has a quarternary ammonium salt connected thereto.

4. The apparatus of claim 1 , further comprising a vacuum pump which is connected to the waste container, the synthesizing container and the collection container to selectively form a vacuum therein for flowing one or more of the F-18 radioactive isotope, the transmitting gas, the cleansing liquid, and at least one of the at least one reagent.

5. The apparatus of claim 1 , wherein the labeling cartridge, the separation cartridge, the connection tube, and the plurality of control valves are formed in a type of a removable cassette which can be selectively attached or detached.

6. The apparatus of claim 2 , wherein the controller controls the plurality of control valves, the first heating unit, and the second heating unit so as to sequentially perform:
making F-18 radioactive isotope pass through the labeling cartridge and then flow into the waste liquid container;
making the transmitting gas pass through the labeling cartridge and then flow into the waster liquid container;
making the cleaning liquid pass through the labeling cartridge and then flow into the waster liquid container;
making the first organic solvent pass through the labeling cartridge and then flow into the waster liquid container;
closing the connection tube connected to the labeling cartridge;
heating the labeling cartridge using the first heating unit;
making the transmitting gas pass through the labeling cartridge so as to cool the labeling cartridge;
making the second organic solvent pass through the labeling cartridge and then flow into the synthesizing container;
heating the synthesizing container using the second heating unit;
making the alkaline aqueous solution flow into the synthesizing container;
making liquid within the synthesizing container pass through the separation cartridge and then flow into the waste liquid container;
making the cleansing liquid pass through the separation cartridge and then flow into the waste liquid container;
making the transmitting gas pass through the separation cartridge and then flow into the waste liquid container; and
making the third organic solvent pass through the separation cartridge and then flow into the collection container.

7. The apparatus of claim 2 , wherein the controller controls the plurality of the control valves and the first heating unit so as to sequentially perform:
making F-18 radioactive isotope pass through the labeling cartridge and then flow into the waste liquid container;
making the transmitting gas pass through the labeling cartridge and then flow into the waster liquid container;
making the cleaning liquid pass through the labeling cartridge and then flow into the waster liquid container;
making the first organic solvent pass through the labeling cartridge and then flow into the waster liquid container;
closing the connection tube connected to the labeling cartridge;
heating the polymer precursor cartridge using the first heating unit;
making the transmitting gas pass through the labeling cartridge so as to cool the polymer precursor cartridge; and
making the third organic solvent pass through the separation cartridge and then flow into the collection container.

8. The apparatus of claim 2 , wherein the controller controls the plurality of the control valves, the first heating unit, and the second heating unit so as to sequentially perform:
making F-18 radioactive isotope pass through the labeling cartridge and then flow into the waste liquid container;
making the transmitting gas pass through the labeling precursor cartridge and then flow into the waster liquid container;
making the cleaning liquid pass through the labeling cartridge and then flow into the waster liquid container;
making the first organic solvent pass through the labeling cartridge and then flow into the waster liquid container;
closing the connection tube connected to the labeling cartridge;
heating the labeling cartridge using the first heating unit;
making the transmitting gas pass through the labeling cartridge so as to cool the labeling cartridge;
making the second organic solvent sequentially pass through the labeling cartridge and the separation cartridge and then flow into the synthesizing container;
making the transmitting gas sequentially pass through the labeling cartridge and the separation cartridge and then flow into the waste liquid container; and
making the third organic solvent pass through the separation cartridge and then flow into the collection container.

Assignees

• Lee Cheol-Soo
• Chi Dae-Yoon
• Heo Eun-Young
• Kim Jong-Min
• Lee Byoung-Se
• Kil Hee-Seup
• Univ Sogang Res Foundation

Inventors

• Lee Cheol-Soo
• Chi Dae-Yoon
• Heo Eun-Young
• Kim Jong-Min
• Lee Byoung-Se
• Kil Hee-Seup

Classifications

• B01J2219/00164

  controlling the flow · CPC title

• B01J19/004 Primary

  Multifunctional apparatus for automatic manufacturing of various chemical products (sequential reactions B01J19/0046) · CPC title

• C07B59/00

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title

• A61J1/2089

  Containers or vials which are to be joined to each other in order to mix their contents (combinations of vial and syringe for mixing their contents A61J1/2096) · CPC title

• A61J3/002

  Compounding apparatus specially for enteral or parenteral nutritive solutions (bottling liquids B67C) · CPC title