Method for the use of [11C] carbon monoxide in labeling synthesis of 11C-labelled amides using metal amides and photo-induced free radical carbonylation
AssigneeGe Healthcare Limited
InventorsOleksiy Itsenko, Tor Kihlberg, Bengt Langstrom
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Abstract
Methods and reagents for photo-initiated carbonylation with carbon-isotope labeled carbon monoxide using weakly nucleophilic amines and alkyl/aryl iodides are provided. The resultant carbon-isotope labeled amides are useful as radiopharmaceuticals, especially for use in Positron Emission Tomography (PET). Associated kits for PET studies are also provided.
Claims18
A method for labeling synthesis, comprising:
- (a) providing a UV reactor assembly comprising a high pressure reaction chamber, a UV lamp and a concave mirror, wherein the high pressure reaction chamber having a window facing the concave mirror, a liquid inlet and a gas inlet in a bottom surface thereof,
- (b) reacting a solution of weakly nucleophilic amine with a metal base to improve the reactivity of said weakly nucleophilic amine,
- (c) adding a solution of akyl or aryl iodides to the solution of step (b) to give a solution 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 into the reaction chamber via the liquid inlet,
- (f) turning on the UV lamp and waiting for a predetermined time while the labeling synthesis occur, and
- (g) collecting the labeled amide from the reaction chamber.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (II) which is pretreated with a metal base of formula MB:
- to give a labeled amide of formula (III):
- wherein R is linear or cyclic alkyl or substituted alkyl, aryl or substituted aryl and R′ and R″ are independently H, linear or cyclic alkyl, or substituted alkyl, aryl or substituted aryl, M is selected from a list comprising Li, Na, K, Cs and Mg and B is selected from alkyl, aryl, dicyclohexylamide, diisopropylamide, hexamethyldisilylamide or YMgX, wherein Y is alky or aryl and X is a halogen.
A carbon-isotope labeled compound of formula (III),
- wherein R is linear or cyclic alkyl or substituted alkyl, aryl or substituted aryl and R′ and R″ are independently H, linear or cyclic alkyl, or substituted alkyl, aryl or substituted aryl.
A kit for PET study comprising a carbon-isotope labeled compound of formula (III),
- wherein R is linear or cyclic alkyl or substituted alkyl, aryl or substituted aryl and R′ and R″ are independently H, linear or cyclic alkyl, or substituted alkyl, aryl or substituted aryl.
Dependencies are inferred from the claim text.