Method for the use of [11C] carbon monoxide in labeling synthesis of 11C-labelled ketones by photo-induced free radical carbonylation
AssigneeGe Healthcare Limited
InventorsBengt Langstrom, Oleksiy Itsenko, Tor Kihlberg
Life of this patent
Estimating the term…
Abstract
Methods and reagents for photo-initiated carbonylation with carbon-isotope labeled carbon monoxide using alkyl/aryl iodides with carbanion precursors pretreated by a base are provided. The resultant carbon-isotope labeled ketones, and pharmaceutical acceptable salts and solvates are useful as radiopharmaceuticals, especially for use in Positron Emission Tomography (PET). Associated kits and method for PET studies are also provided.
Claims13
A method for labeling synthesis, comprising:
- (a) providing a UV reactor assembly comprising a high pressure reaction chamber with a gas inlet and a liquid inlet, a UV spot light source with a light guide, wherein the light guide is used to provide photo irradiation of a reaction mixture through a window in the reaction chamber,
- (b) preparing a carbanion solution by reacting a base with a carbanion precursor in a solution,
- (c) adding an alkyl or aryl iodide to the carbanion solution of step (b) to give a reagent volume to be labeled,
- (d) introducing a carbon-isotope monoxide enriched gas-mixture into the reaction chamber of the UV reactor assembly via the gas inlet,
- (e) introducing at high pressure said reagent volume into the reaction chamber via the liquid inlet,
- (f) turning on the UV spot light source and waiting for a predetermined time while the labeling synthesis occur, and
- (g) collecting the labeled ketone from the reaction chamber.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a carbanion precursor of formula (II) HCR′R″R′″, which is pretreated with a base:
- RI (I) to give a labeled ketone of formula (III):
- wherein R is linear or cyclic alkyl or substituted alkyl, aryl or substituted aryl;
- H is acidic hydrogen;
- R′,R″ and R′″ are H, linear or cyclic alkyl, or substituted alkyl, aryl or substituted aryl, and may contain chloro and fluoro groups, and one or more of the groups R′, R″ and R′″ have a feature that stabilizes the negative charge on the C atom of the newly formed carbanion;
- and the base is any organic or inorganic compound that produces necessary carbanion upon reacting with a carbanion precursor.
A carbon-isotope labeled compound of formula (III), and pharmaceutically acceptable salts and solvates thereof:
- wherein R is linear or cyclic alkyl or substituted alkyl, aryl or substituted aryl;
- H is acidic hydrogen;
- R′,R″ and R′″ are H, linear or cyclic alkyl, or substituted alkyl, aryl or substituted aryl, and may contain chloro and fluoro groups, and one or more of the groups R′, R″ and R′″ has a feature that stabilizes the negative charge on the C atom.
Dependencies are inferred from the claim text.