Synthesis of [¹¹C‐carbonyl]hydroxyureas by a rhodium‐mediated carbonylation reaction using [¹¹C]carbon monoxide

Abstract [ 11 C]Hydroxyurea has been successfully labelled using [ 11 C]carbon monoxide at low concentration. The decay‐corrected radiochemical yield was 38±3%, and the trapping efficiency of [ 11 C]carbon monoxide in the order of 90±5%. This synthesis was performed by a rhodium‐mediated carbonylation reaction starting with azidotrimethylsilane and the rhodium complex being made in situ by chloro(1,5‐cyclooctadiene)rhodium(I) dimer ([Rh(cod)Cl] 2 ) and 1,2‐ bis (diphenylphosphino)ethane (dppe). ( 13 C)Hydroxyurea was synthesized using this method and the position of the labelling was confirmed by 13 C‐NMR. In order to perform accurate LC–MS identification, the derivative 1‐hydroxy‐3‐phenyl[ 11 C]urea was synthesized in a 35±4% decay‐corrected radiochemical yield. After 13 µA h bombardment and 21 min synthesis, 1.6 GBq of pure 1‐hydroxy‐3‐phenyl[ 11 C]urea was collected starting from 6.75 GBq of [ 11 C]carbon monoxide and the specific radioactivity of this compound was in the order of 686 GBq/µmol (3.47 nmol total mass). [ 11 C]Hydroxyurea could be used in conjunction with PET to evaluate the uptake of this anticancer agent into tumour tissue in individual patients.