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Title:
METHOD FOR PREPARING FLUORINE-18-LABELED FLUOROMETHYL-SUBSTITUTED RADIOPHARMACEUTICALS USING SELECTIVE AZIDE SUBSTITUTION REACTION AND PRECURSOR SCAVENGING
Document Type and Number:
WIPO Patent Application WO/2020/059986
Kind Code:
A1
Abstract:
The present invention relates to a method for preparing a fluorine-18-labeled fluoromethyl-substituted radiopharmaceutical using selective azide substitution reaction, the method comprising: a first step for obtaining [18F]fluoride from a cyclotron through a 18O(p, n)18F reaction; a second step for obtaining a [18F]F-/H2 18O solution by separating the [18F]fluoride using an acetonitrile reaction solution in which K2.2.2 and K2CO3 are dissolved; a third step for obtaining K2.2.2/K18F by heating the [18F]F-/H2 18O solution; a fourth step for obtaining a first precursor solution by adding the K2.2.2/K18F and a bistoxyloxymethane compound into a reactor and adding a reaction solvent thereto to cause reaction; a fifth step for obtaining a [18F]fluoromethyltosylate compound by cooling the first precursor solution and adding an azide reagent thereto to cause azide substitution reaction; a sixth step for obtaining a second precursor solution by adding a bioactive molecule precursor to the [18F]fluoromethyltosylate compound to cause alkylation reaction; and a seventh step for preparing a fluorine-18-labeled fluoromethyl-substituted radiopharmaceutical without a HPLC separation process by adding a precursor scavenger to the second precursor solution to remove unreacted precursors. According to the present invention, in the synthesis process of a radiopharmaceutical, by non-activating an excess amount of a bistoxyloxymethane compound present in a reaction mixture through selective azide substitution reaction and remarkably enhancing a yield of alkylation between the bioactive molecule precursor and the [18F]fluoromethyltosylate compound in the subsequent step, a fluorine-18-labeled fluoromethyl-substituted radiopharmaceutical with high radiochemical purity can be synthesized even when HPLC separation and purification processes are omitted, and thus manufacturing time and manufacturing costs due to the HPLC process can be reduced.

Inventors:
LEE BYUNG CHUL (KR)
LU YING QING (CN)
JO BYEONG MIN (KR)
Application Number:
PCT/KR2019/002862
Publication Date:
March 26, 2020
Filing Date:
March 13, 2019
Export Citation:
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Assignee:
BIO IMAGING KOREA CO LTD (KR)
International Classes:
C07B59/00; A61K51/04
Foreign References:
KR20140076575A2014-06-20
KR20140069001A2014-06-09
JP5595903B22014-09-24
KR20140113622A2014-09-24
Other References:
KIM, HYE LAN ET AL.: "F-18 labeled RGD probes based on bioorthogonal strain-promoted dick reaction for PET imaging", ACS MEDICINAL CHEMISTRY LETTERS, vol. 6, 2015, pages 402 - 407, XP055250584, DOI: 10.1021/ml500464f
CAS, no. 1180485-67-9
See also references of EP 3842405A4
Attorney, Agent or Firm:
KANG, Tae Hoon et al. (KR)
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