Routine synthesis of N-[11C-methyl]scopolamine by phosphite mediated reductive methylation with [11C]formaldehyde

A synthesis of [11C]scopolamine capable of clinical delivery of this agent in high specific activity is described. The precursor [11C]formaldehyde was produced by catalytic oxidation of [11C]CH3OH over metallic silver and was used to N-11C-methylate norscopolamine using aqueous neutral potassium phosphite as the reducing agent. The labeling reaction was complete after 5 min at 75-80[deg]C and the [11C]scopolamine (99% radiochemical purity) was isolated by preparative HPLC. Total synthesis time is less than 45 min. Decay corrected radiochemical yields from [11C]CO2 are presently 20-43%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27552/1/0000596.pd

Extraction of [18F]fluoride from [18O]water by a fast fibrous anion exchange resin

[18F]Fluoride for nucleophilic radiofluorination was recovered from target water by trapping on a fibrous anion exchange resin in the hydroxide form and subsequent displacement into wet methanolic K2CO3. Extraction into methanol facilitated rapid evaporation and resolubilization of the [18F]fluoride as an ion pair. The resin was first dried in situ and rehydrated with [18O]H2O to avoid isotopic dilution of the target water.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28900/1/0000737.pd

Routine production of 2-deoxy-2-[18F]fluoro--glucose by direct nucleophilic exchange on a quaternary 4-aminopyridinium resin

Resin-supported [18F]fluoride ion has been prepared and applied to a rapid, convenient synthesis of [18F]FDG. "No-carrier-added" [18F]fluoride ion is collected on a quaternary 4-(N, N-dialkylamino)-pyridinium functionalized polystyrene anion exchange resin directly from a [18O]water target, dried by rinsing with acetonitrile, and then reacted with 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-[beta]--mannopyrannose. Acidic hydrolysis yields [18F]FDG in a synthesis time of 40 min with overall yields presently averaging above 50%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28859/1/0000694.pd

Multiphase extraction: Rapid phase-transfer of [18F]fluoride ion for nucleophilic radiolabeling reactions

In multiphase extraction [18F]fluoride ion for radiolabeling is recovered from target water by passage through a small column of microporous polymer impregnated with a lipophilic cryptand or quaternary ammonium salt. The 18O enriched water can be recovered for reuse. The [18F]fluoride ion-pair is eluted from the column by a small volume of acetonitrile or other organic solvent. Evaporation of the acetonitrile removes traces of water to yield a reactive ion pair for nucleophilic radiofluorination reactions. A wide range of ion-pairs based on K+ or NH4+ cryptands or quaternary ammonium salts can be employed. The method was applied to the synthesis of [18F]FDG.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27603/1/0000647.pd

A captive solvent method for rapid N-[11C]methylation of secondary amides: Application to the benzodiazepine, 4'-chlorodiazepam (RO5-4864)

[11C]4'-Chlorodiazepam (RO5-4864), for PET studies of peripheral benzodiazepine receptors, was synthesized by alkylation of 1-desmethyl-4'-chlorodiazepam, in a small volume of acetone adsorbed on acrylic yarn, with [11C]methyl iodide in the injection loop of a liquid chromatograph. The reaction mixture was introduced directly onto a small, disposable alumina chromatographic column. Elution with pentane:ethanol gave a product of high chemical and radiochemical purity. A simple heating and cooling device for the injection loop is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27565/1/0000609.pd

Some recent approaches to smaller, faster devices for remote PET radiolabeling

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90295/1/25802601204_ftp.pd

High yield synthesis of high specific activity R-(-)-[11C]epinephrine for routine PET studies in humans

R-(-)-[11C]Epinephrine ([11C]EPI) has been synthesized from R-(-)-norepinephrine by direct methylation with [11C]methyl iodide or [11C]methyl triflate. The total synthesis time including HPLC purification was 35-40 min. The radiochemical yields (EOB) were 5-10% for [11C]methyl iodide and 15-25% for [11C]methyl triflate. Radiochemical purity was >98%; optical purity determined by radio-chiral HPLC was >97%. The [11C]methyl triflate technique produces R-(-)-[11C]epinephrine in quantities (80-170 mCi) sufficient for multiple positron emission tomography studies in humans. The two synthetic methods are generally applicable to the production of other N-[11C]methyl phenolamines and N-[11C]methyl catecholamines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30501/1/0000129.pd