Ali M. Emran

Cerebral metabolic effects of a verbal fluency test: A PET scan study

Sixteen normal volunteers were studied with [F-18] fluorodeoxyglucose and positron emission tomography scans during behavioral activation with a verbal fluency test, and 35 age-matched controls were studied with resting-state scans. There was an overall increase of the cerebral glucose metabolic rate of 23.3% during verbal fluency activation, compared to the resting state, with the greatest activation in bilateral temporal and frontal lobes. A negative correlation between test performance scores and indices of metabolism was found in frontal, temporal, and parietal regions. Damage to the left frontal lobe maximally affects scores on verbal fluency tests, but performing the test activates a network of regions, of which the left frontal lobe is only one. Proficient performance in verbal fluency seems to require less metabolic activation than poor performance, perhaps because of the efficiency of cognitive strategies employed.

1-[11C]Butanol: Synthesis and development as a radiopharmaceutical for blood flow measurements☆

Abstract 1-[ 11 C]Butanol was synthesized via two routes: carbonylation of an organoborane and carbonation of a Grignard reagent. The reaction of 11 CO with B- n -propyl-9-borabicyclo[3.3.1]nonane, followed by oxidation in alkaline medium, produced 1-[ 11 C]butanol in 33–71% yield (EOB) in 60 min. The reaction of 11 CO 2 with 1-propylmagnesium bromide, followed by a lithium aluminum hydride reduction, produced 1-[ 11 C]butanol in 55–74% yield (EOB) in 25–27 min. The radiochemical purity was 95–99% in each case.

Syntheses with isotopically labelled carbon. Methyl iodide, formaldehyde and cyanide

Many of the uniquely labelled synthetic precursors currently employed in the design of sophisticated radiolabelled compounds have their origins in the field of hot atom chemistry. Particularly, the development during the past few years of automated, on-line synthetic procedures which combine the nuclear reaction, hot atom and classical chemistry, and rapid purification methods has allowed the incorporation of useful radionuclides into suitable compounds of chemical and biochemical interest. The application of isotopically labelled methyl iodide, formaldehyde, and cyanide anion as synthetic intermediates in research involving human physiology and nuclear medicine, as well as their contributions to other scientific methodology, is reviewed.

Preparation of 11C-Urea from No-carrier-added 11C-Cyanide☆

Abstract Carbon-11 labeled urea was synthetized by thermal transformation of 11 C-labeled ammonium cyanate. The 11 C-cyanate was prepared by oxidation of 11 C-cyanide. The total synthesis was accomplished in 20 min starting from 11 CN − to obtain 11 C-urea in 85±5% radiochemical yield with purity greater than 98%. HPLC was utilized to examine the various reactants and products.

Synthesis of nitrogen-13 labeled alkylamines via amination of organoboranes

Organoboranes react with nitrogen-13 labeled ammonia to produce alkylamines in moderate yield. When 13N labeled ammonia was bubbled into a tetrahydrofuran solution containing 0.5M tridecylborane, 1-[13N]aminodecane was formed in 25-30 min from the end of bombardment (EOB) in 40-60% overall yield. 1-[13N]aminooctane and 1-[13N]aminohexane were also synthesized from appropriate organoboranes in similar yield.

Optimized production of high specific activity [11C]urea.

Abstract Use of [ 11 C]urea as an intermediate for the preparation of “no-carrier-added” radiopharmaceuticals required optimization of synthetic parameters. A procedure has been developed to produce [ 11 C]urea from “no-carrier-added” 11 CN − within 16 ± 1 min from end of bombardment (EOB) with a radiochemical yield of 95.0 ± 2.5%.

Use of 11C as a tracer for studying the synthesis of radiolabelled compounds—II: 2-[11C]-5,5-diphenylhydantoin from [11C]cyanide☆

Carbon-11 was used as a tracer to study the various physical and chemical parameters involved in the synthesis of 2-[11C]-5,5-diphenylhydantoin (DPH) starting from high specific activity [11C]urea. To optimize the reaction conditions, the effects of reaction time, temperature as well as various reactant concentrations were studied. High performance liquid chromatography (HPLC) and thin layer chromatography (TLC) were used to determine the reactants and products and to monitor progress of the reactions. The [11C]DPH was isolated within 55–60 min from end of bombardment (EOB) by preparative HPLC in an overall 30–35% yield with a radiochemical purity of 98.2 ± 0.5% and a specific activity as high as 3.2 ± 0.3 Ci/μmol (EOB).

Use of 11C as a tracer for studying the synthesis of [11C]urea from [11C]cyanide.

The use of reversed-phase liquid chromatography and radiochemical detection with carbon-11 (t1/2 = 20.4 min) as a tracer allowed the study of the preparation of [11C]urea from [11C]cyanide at no-carrier-added concentrations. [11C]cyanate was readily prepared by permanganate oxidation of [11C]cyanide at 75 degrees C. The conversion of NH4O11CN (approximately 0.03 mM) to [11C]urea in the presence of excess ammonium ions (0.28 M) was found to best fit pseudo first order reaction kinetics with a rate constant of 0.065 +/- 0.008 min-1 at 75 degrees C. Heating at higher temperatures (180-200 degrees C) revealed that the conversion of NH4O11CN to [11C]urea occurred in high yield in less than 3 min. The hydrolysis of [11C]cyanate to [11C]carbonate, a possible side reaction, was found to proceed at a rate of 0.010 +/- 0.001 min-1 at 113 degrees C.

Use of liquid chromatography for separation and determination of carrier species associated with the synthesis of no carrier-added11C-labelled compounds determination of the specific activity of {11C} urea

An analytical technique using reversed-phase liquid chromatography has been developed for the determination of urea at quantities as low as 1 ng to quantitate the amount of non-labelled urea produced during the synthesis of no-carrier-added {11C}urea starting from11CN−. As a result, the specific activity of the {11C} urea thus prepared was calculated to be as high as 3.5±0.8 Ci/μmol.

Carbon-11 labeled dialkylketones: synthesis of 9-[11C]heptadecan-9-one.

9-[11C]heptadecan-9-one was synthesized from di-n-octylthexylborane via cyanidation with K11CN. The rearrangement of the organoborane intermediate followed by alkaline oxidation produced the title compound in 55-60 min from the end of bombardment (EOB) in 50-70% overall yield. The reaction sequence is applicable for the synthesis of various dialkyl ketones.