Stabilized radiolabelling reaction

Patent metadata

Field	Value
Publication number	US-11565257-B2
Application number	US-201917043445-A
Country	US
Kind code	B2
Filing date	Mar 29, 2019
Priority date	Mar 29, 2018
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

The present invention provides a method for the synthesis of an injectable composition comprising a [ 18 F]-labelled pyridaben derivative that is advantageous over prior methods. In particular, the method of the present invention comprises a method of radiosynthesis that permits a more facile purification using solid phase extraction (SPE).

First claim

The invention claimed is:

1. A method for production of an 18 F-labelled radiotracer compound comprising in an automated cassette system:
reacting a precursor compound with 18 F-fluoride in the presence of (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO) and acetonitrile (MeCN) to obtain the 18 F-labelled compound wherein:
said precursor compound is of Formula I:
BTM-LINKER-LG (I)
wherein:
BTM is an analogue of pyridaben;
LINKER is an alkylene or an alkoxyalkylene; and,
LG is a sulfonate-containing leaving group; and

said 18 F-labelled compound is of Formula II:
BTM-LINKER- 18 F (II)

wherein BTM and LINKER are as defined for Formula I;
purifying said 18 F-labelled compound by means of a first solid phase extraction (SPE) cartridge in the automated cassette system, wherein said purification does not comprise high performance liquid chromatography (HPLC); and
eluting the 18 F-labelled radiotracer from a second SPE cartridge wherein the starting radioactivity is at least 100 GBq.

2. The method as defined in claim 1 wherein said precursor compound is a compound of Formula Ia:

and said 18 F-labelled compound is a compound of Formula Ila:

wherein:
R1 is an optionally substituted C1-6 alkyl;
R2 is hydrogen or halo;
W is an optionally substituted alkylene or heteroalkylene;
LINKER and LG are as defined in claim 1 .

3. The method as defined in claim 2 wherein R 1 is C 1-6 alkyl.

4. The method as defined in claim 2 wherein R 1 is methyl, ethyl, propyl, n-butyl, s-butyl, or t-butyl.

5. The method as defined in claim 2 wherein R 2 is halo.

6. The method as defined in claim 2 wherein R 2 is chloro.

7. The method as defined in claim 2 wherein W is heteroalkylene.

8. The method as defined in claim 2 wherein W is alkoxyalkylene.

9. The method as defined in claim 1 wherein said compound of Formula I is a compound of Formula Ib:

and said compound of Formula II is a compound of Formula IIb:

R 1 is an optionally substituted C 1-6 alkyl;
R 2 is hydrogen or halo;
LINKER is an alkylene or an alkoxyalkylene; and,
LG is a sulfonate-containing leaving group.

10. The method as defined in claim 1 wherein said compound of Formula I is:

wherein LG is a sulfonate-containing leaving group;
and said compound of Formula II is:

11. The method as defined in claim 1 wherein LG is selected from mesylate, tosylate, triflate, nosylate, or 1,2-cyclic sulfate.

12. The method as defined in claim 11 wherein LG is tosylate.

13. The method as defined in claim 1 wherein said precursor compound is dissolved in acetonitrile.

14. The method as defined in claim 1 wherein said TEMPO is present in a molar ratio to the precursor compound of between 0.01:1 and 5:1.

15. The method as defined in claim 1 wherein the starting radioactivity is between 100-1000 GBq.

16. The method as defined in claim 15 wherein the starting radioactivity is between 100-750 GBq.

Assignees

• Ge Healthcare Ltd

Inventors

• Engell Torgrim
• Jackson Alexander
• Khan Imtiaz Ahmed
• Clarke Alan Peter
• Mcrobbie Graeme
• Grigg Julian

Classifications

• C07B59/002 Primary

  Heterocyclic compounds · CPC title

• C07B2200/05

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

• B01L2200/0631

  Purification arrangements, e.g. solid phase extraction [SPE] · CPC title

• B01J19/004

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

• B01L3/502753 Primary

  characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation · CPC title