US 2023/0416293 A1 · SYNTHESIS OF [18F]-LABELED THYMIDINE ANALOGUES

Abstract

Thymidine analogues, 5-substituted 2′-deoxy-2′-[18F]fluoro-arabinofuranosyluracil derivatives, are promising positron emission tomography (PET) tracers being evaluated for noninvasively imaging cancer cell proliferation and/or reporter gene expression. We report the radiosynthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-d-arabinofuranosyluracil ([18F]FMAU) and other 2′-deoxy-2′-[18F]fluoro-5-substituted-1-β-d-arabinofuranosyluracil analogues using 1,4-dioxane to replace the currently used 1,2-dichloroethane. Compared to 1,2-dichloroethane, 1,4-dioxane is analyzed as a better solvent in terms of radiosynthetic yield and toxicity concern. The use of a less toxic solvent allows for the translation of the improved approach to clinical production. The new radiolabeling method can be applied to an extensive range of uses for 18F-labeling of other nucleoside analogues.

Claims14

Dependent claims

A method of synthesizing 2′-deoxy-2′-[18F]-fluoro-5-substituted-1-β-D-arabinofuranosyl-uracil or cytosine compounds in one-pot comprising:

a) radiolabeling a precursor sugar with 18F;
b) contacting the 18F radiolabeled sugar with a silylated uracil or cytosine in the presence of 1,4-dioxane, trimethylsilyl trifluoromethylsulfonate (TMSOTf), and hexamethyldisilazane (HMDS);
c) incubating the components in step (b) under conditions that allow for conjugation of the 18F radiolabeled sugar and the silylated uracil or cytosine;
and
d) removing the protecting groups of the components in step (c);
wherein steps a) to d) are performed in one-pot.

3 more elements

A method of synthesizing an [18F]-labeled 2′-deoxy-arabino 5-substituted or unsubstituted uracil or cytosine nucleoside in one-pot comprising:

a) radiolabeling a precursor sugar with 18F;
b) contacting the 18F radiolabeled sugar with a silylated uracil or cytosine in the presence of 1,4-dioxane, trimethylsilyl trifluoromethylsulfonate (TMSOTf), and hexamethyldisilazane (HMDS);
c) incubating the components in step (b) under conditions that allow for conjugation of the 18F radiolabeled sugar and the silylated uracil or cytosine derivatives;
and
d) removing the protecting groups of the components in step (c);
wherein steps a) to d) are performed in one-pot.

3 more elements

Dependencies are inferred from the claim text.

Synthesis of [18f]-labeled thymidine analogues

Life of this patent

Synthesis of [18f]-labeled thymidine analogues

Life of this patent

Abstract

Claims14