ABSTRACT
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.
Subject(s)
Epinephrine/chemical synthesis , Isotope Labeling/methods , Carbon Radioisotopes , Chromatography, High Pressure Liquid , Epinephrine/isolation & purification , Humans , Norepinephrine/chemistry , Norepinephrine/isolation & purification , Stereoisomerism , Tomography, Emission-ComputedABSTRACT
Carbon-11-labeled meta-hydroxyephedrine (HED, N-methyl-metaraminol) is a catecholamine analog developed for the PET imaging of sympathetic nerve terminals of the heart. The retention mechanisms of this tracer and interactions with norepinephrine were investigated in isolated working rat hearts. Externally monitored time-activity curves showed a strong uptake process in control hearts (K1 = 2.66 +/- 0.39 ml/g/min) and relatively slow monoexponential clearance rates (k2 = 0.011 +/- 0.003 min-1). Comparative studies with the neuronal uptake inhibitor desipramine indicated little extraneuronal distribution and a strong dependence of clearance rate on neuronal reuptake of tracer. Norepinephrine (< or = 10 nM) increased HED clearance rate without affecting initial uptake rates. This effect may be related to competitive inhibition of neuronal reuptake and/or accelerated neuronal release of HED. These results indicate that the uptake and retention of HED by the myocardium is highly specific to sympathetic nerve terminals. However, its retention in the myocardium is not directly related to neuronal processing of catecholamines (i.e., metabolism and vesicular turnover). Thus, important differences may exist in the physiologic information indicated by retention measurements of HED and radiolabeled catecholamines. The finding of increased clearance rates with NE in the perfusion medium recommends the consideration of potential effects of circulating and endogenous catecholamines on PET measurements of myocardial retention of HED, especially in subjects with elevated plasma catecholamines or high sympathetic tone.
Subject(s)
Carbon Radioisotopes , Ephedrine/analogs & derivatives , Heart/diagnostic imaging , Myocardium/metabolism , Norepinephrine/pharmacology , Animals , Ephedrine/pharmacokinetics , Female , Heart/drug effects , Hemodynamics/drug effects , In Vitro Techniques , Radionuclide Imaging , Rats , Rats, Sprague-DawleyABSTRACT
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-D-mann opyrannose. Acidic hydrolysis yields [18F]FDG in a synthesis time of 40 min with overall yields presently averaging above 50%.
Subject(s)
Deoxy Sugars , Deoxyglucose , Fluorine Radioisotopes , Isotope Labeling/methods , Anion Exchange Resins , Deoxyglucose/analogs & derivatives , Fluorodeoxyglucose F18ABSTRACT
[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.
Subject(s)
Fluorine Radioisotopes/isolation & purification , Oxygen Isotopes , Water/analysis , Anion Exchange ResinsABSTRACT
The false neurotransmitter metaraminol has been 18F labeled and evaluated as a possible heart imaging agent on the basis of its selective accumulation in adrenergic nerves. Reaction of 6-(acetoxymercurio)-N-t-BOC-metaraminol with acetyl hypofluorite followed by removal of the BOC group provides a regiospecific synthesis of 6-fluorometaraminol (4). Use of acetyl hypo[18F]fluorite gives [18F]-4 in 60 min in 20-42% radiochemical yield. Systemic blockade of the neuronal uptake-1 carrier with desmethylimipramine or systemic destruction of the adrenergic nerves with 6-hydroxydopamine lowers [18F]-4 accumulation greater than or equal to 85% in all four regions of the rat heart. These preliminary findings suggest that [18F]-4 could be used to assess neuronal damage in various heart diseases by positron emission tomography.
Subject(s)
Fluorine Radioisotopes , Heart/innervation , Metaraminol/analogs & derivatives , Sympathetic Nervous System/diagnostic imaging , Animals , Dogs , Female , Heart/diagnostic imaging , Male , Metaraminol/chemical synthesis , Radionuclide Imaging , Rats , Rats, Inbred StrainsABSTRACT
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 degrees 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%.
Subject(s)
Carbon Radioisotopes , Parasympatholytics/chemical synthesis , Phosphites , Potassium Compounds , Scopolamine Derivatives/chemical synthesis , Formaldehyde , Humans , Isotope Labeling/methods , N-Methylscopolamine , Phosphorous Acids , Receptors, Muscarinic , Tomography, Emission-ComputedABSTRACT
[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.
Subject(s)
Benzodiazepinones , Carbon Radioisotopes , Isotope Labeling/methods , Time Factors , Tomography, Emission-ComputedABSTRACT
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 NH+4 cryptands or quaternary ammonium salts can be employed. The method was applied to the synthesis of [18F]FDG.
