Preparation of 18F-fluciclovine

Patent metadata

Field	Value
Publication number	US-10023525-B2
Application number	US-201615173839-A
Country	US
Kind code	B2
Filing date	Jun 6, 2016
Priority date	Aug 9, 2012
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

The present invention provides a method for the production of [18F]-FACBC which has advantages over know such methods. Also provided by the present invention is a system to carry out the method of the invention and a cassette suitable for carrying out the method of the invention on an automated radiosynthesis apparatus.

First claim

What is claimed is:

1. A system for carrying out a method to prepare 1-amino-3-[ 18 F]-fluorocyclobutanecarboxylic acid ([ 18 F]-FACBC) comprising:
(a) a solid phase having compound of Formula II adsorbed on its surface

wherein:
PG 1 is a carboxy protecting group; and,
PG 2 is an amine protecting group;

(b) a source of PG 1 deprotecting agent to be reacted with said compound of Formula II;
(c) a source of elution solution to be passed through said solid phase to obtain an eluted compound of Formula III:

(d) a source of PG 2 deprotecting agent to be reacted with said compound of Formula III to obtain a reaction mixture comprising [ 18 F]-FACBC;
(e) a reaction container; and,
(f) a waste means;
wherein said system further comprises means permitting sequential flow from:
(i) (e) to (a);
(ii) (b) to (a);
(iii) (a) to (f);
(iv) (c) to (e) via (a); and,
(v) (d) to (e).

2. The system as defined in claim 1 wherein said compound of Formula II is a compound of Formula IIa:

wherein PG 1 and PG 2 are as defined in claim 1 .

3. The system as defined in claim 1 wherein PG 1 is ethyl.

4. The system as defined in claim 1 wherein PG 2 is t-butoxycarbonyl.

5. The system as defined in claim 1 wherein said solid phase is a tC18 solid phase extraction (SPE) column.

6. The system as defined in claim 1 wherein said PG 1 deprotecting agent is NaOH.

7. The system as defined in claim 1 wherein said PG 2 deprotecting agent is HCl.

8. The system as defined in claim 1 wherein said elution solution is water.

9. The system as defined in claim 1 further comprising a hydrophilic lipophilic balanced (HLB) solid phase to purify said 1-amino-3-[18F]-fluorocyclobutanecarboxylic acid.

10. The system as defined in claim 9 further comprising a second purification means comprising an alumina solid phase.

11. The system as defined in claim 1 wherein said system is suitable for use with an automated radiosynthesis apparatus.

12. A system for carrying out said method to prepare 1-amino-3-[ 18 F]-fluorocyclobutanecarboxylic acid ([ 18 F]-FACBC) comprising the system as defined in claim 1 and further comprising:
(g) a source of a precursor compound of Formula I

wherein:
LG is a leaving group;
PG 1 as defined in claim 1 ; and,
PG 2 is as defined in claim 1 ; and,

(h) a source of [ 18 F]fluoride.

13. The system as defined in claim 12 wherein said compound of Formula I is a compound of Formula Ia:

wherein LG is as defined in claim 12 , PG 1 is as defined in claim 1 , and PG 2 is as defined in claim 1 .

14. The system as defined in claim 12 wherein LG is trifluoromethanesulfonate.

15. A cassette comprising the system as defined in claim 9 for use on an automated synthesis apparatus.

16. A cassette comprising the system as defined in claim 1 for use on an automated synthesis apparatus.

17. A cassette comprising the system as defined in claim 10 for use on an automated synthesis apparatus.

Assignees

• Ge Healthcare Ltd

Inventors

• Svadberg Anders
• Ryan Olav
• Smeets Roger

Classifications

• C07C269/06

  by reactions not involving the formation of carbamate groups · CPC title

• C07B59/001

  Acyclic or carbocyclic compounds · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07C2601/04

  with a four-membered ring · CPC title

• B01J19/24

  Stationary reactors without moving elements inside (B01J19/08, B01J19/26 take precedence; with stationary particles B01J8/02) · CPC title