11C-labeling of busulphan.
Busulphan [1,4-bis(methanesulfonoxy)butane], an alkylating agent used in the treatment of chronic myelocytic leukemia, was labeled with the positron-emitting radionuclide carbon-11 in a four-step synthetic procedure [1-11C]4-Hydroxybutyronitrile was obtained in 60-70% yield by the reaction of [11C]cyanide with 3-bromopropanol. The nitrile was hydrolysed to [1-11C]gamma-butyrolactone (80-90% yield) with sulfuric acid. Solid phase extraction was used to isolate the lactone and change the solvent before reduction to [1-11C]1,4-butanediol. Dimesylation of the diol with methanesulfonyl chloride in dichloromethane/pyridine yielded [1-11C]busulphan with conversions in the order of 30-35%. The total time of synthesis, including HPLC purification, was 65-75 min from the end-of-trapping of [11C]ammonium cyanide. The decay-corrected isolated yield of no-carrier-added [11C]busulphan was 4-7% and the radiochemical purity was better than 99%.
Hassan
M
M
Karolinska Pharmacy, Stockholm, Sweden.
Thorell
J O
JO
Warne
N
N
Stone-Elander
S
S
D002066:Busulfan / Q000737:chemistry* / Q000302:isolation & purification; D002250:Carbon Radioisotopes / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003486:Cyanides / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods*
D002250:Carbon Radioisotopes; D003486:Cyanides; C026524:ammonium cyanide; D002066:Busulfan