Maximum Radiochemical Yield Research Articles

Radioiodination, purification and bioevaluation of Piroxicam in comparison with Meloxicam for imaging of inflammation

The present study is performed to compare the electrophilic substitution radioiodination reaction of two non-steroidal anti-inflammatory drugs namely, Piroxicam (Pirox) and Meloxicam (Melox) with 125I where both chloramine-T (CAT) and iodogen were used as oxidizing agents. The factors affecting the percent of radiochemical yields such as drug concentration, pH of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media were studied to optimize the conditions for labeling of Pirox and Melox and to obtain high radiochemical yields. The maximum radiochemical yield of 125I-Piroxicam (125I-Pirox) was 94% using 3.7 MBq of Na125I, 0.4 mM of Pirox as substrate, 3.6 mM of chloramine-T (CAT) as oxidizing agent in acetone at neutral pH = 7 and at 60 °C within 20 min where the maximum radiochemical yield of 125I-Melox was 92% using 0.7 mM of Melox as substrate, 0.62 mM of iodogen as oxidizing agent in acetone at neutral pH = 7 and at 25 °C within 30 min. The radiochemical yields were determined by TLC and high-pressure liquid chromatography (HPLC). Tracers showed good localization in inflamed muscle either septic or sterile. The collected data indicates that Pirox and Melox can be used as antiinflammatory imaging agents at 24 and 2 h post injection, respectively.

Simple and convenient radiolabeling of proteins using a prelabeling-approach with thiol-DOTA

Commonly applied methods for radiometal-labeling of proteins require complex and protracted derivatization reactions of the protein and the subsequent radiolabeling is time-consuming due to the low reaction temperatures applicable. Therefore, a convenient and efficient prelabeling technique for proteins using the DOTA derivative 2,2′,2′′-(10-(2-(2-mercaptoethylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (thiol-DOTA) containing a thiol moiety for rapid and selective introduction into maleimide-derivatized proteins was developed. Thiol-DOTA was labeled with 68Ga, 90Y and 177Lu and subsequently introduced into bovine serum albumin and a human IgG with maximum radiochemical yields of 66%. The entire radiolabeling procedure was completed after only 30 min making this a favorable new labeling technique for proteins.

An investigation of the 125I‐radioiodination of colchicine for medical purposes

AbstractA procedure for radioiodination of colchicine with iodine‐125 is carried out via an electrophilic substitution reaction. The reaction parameters studied were colchicine concentration, pH of the reaction mixture, reaction time, temperature, different oxidizing agents and different organic media to optimize the conditions for the labeling of colchicine and to obtain a high radiochemical yield of the 125I‐colchicine (125I‐Col). Using 3.7 MBq of Na125I, 1.25 mM of colchicine as substrate, 1.1 mM of chloramine‐T (CAT) as oxidizing agent in ethanol at 60°C for 5 min, a maximum radiochemical yield of 125I‐Col (60%) was obtained. The specific activity of 125I‐Col obtained was 44.4 MBq/0.5 mmol, and the labeled compound was not completely separated and purified from Col by means of high‐pressure liquid chromatography (HPLC), so the uncertainty in the purity may affect the distribution and clearance routes due to the expected competition between 125I‐Col and Col. The biological distribution in normal mice indicates the suitability of radioiodinated colchicine for imaging of muscles. Copyright © 2008 John Wiley & Sons, Ltd.

Nucleophilic substitution of nitro groups by [ 18F]fluoride in methoxy-substituted ortho-nitrobenzaldehydes—A systematic study

As model reactions for the introduction of [ 18F]fluorine into aromatic amino acids, the replacement of NO 2 by [ 18F]fluoride ion in mono- to tetra-methoxy-substituted ortho-nitrobenzaldehydes was systematically investigated. Unexpectedly, the highly methoxylated precursors 2,3,4-trimethoxy-6-nitrobenzaldehyde and 2,3,4,5-tetramethoxy-6-nitrobenzaldehyde showed high maximum radiochemical yields (82% and 48% respectively). When the electrophilicity of the leaving group substituted carbon atom is expressed by its 13C NMR chemical shift a good correlation with the reaction rate at the beginning of the reaction (first min) was found ( R 2 = 0.89), whereas the maximum radiochemical yields correlated much poorer with this electrophilicity parameter. This may be caused by side reactions becoming influencial in the further reaction course. As possible side reactions the demethylation of methoxy groups and intramolecular redox reactions could be detected by HPLC/MS.

Electrochemical radiofluorination. Part 2 . Anodic monofluorination of substituted benzenes using [ 18F]fluoride

Electrochemical fluorination of various monosubstituted aromatic compounds was performed with [ 18F]fluoride using potentiostatic anodic oxidation on platinum electrodes in an undivided cell in acetonitrile with a mixture of Et 3N·3HF/Et 3N·HCl as electrolyte. Maximum radiochemical yields were obtained after a charge of 50 C passed the solution. The results showed a clear dependence of the radiochemical yields on the oxidation potentials E 1/2 of the substrates as a consequence of different substituents namely CH 3CO-, F-, Cl-, Br- and tert.-Butyl. With increasing E 1/2, the fluorination yields decreased from 7.9% ( tert.-butylbenzene) to 1.5% (acetophenone). The ratio between F-for-X substitution and F-for-H substitution correlated with the bond energies of the C–X bond. With higher bond energies, less X-substitution was observed.

Dry state preparation of radioiodine labeled meta-iodobenzylguanidine

Radioiodination of meta-iodobenzylguanidine (MIBG) by the isotopic exchange technique in the dry state has been performed. Benzoic acid, pivalic acid and acetamide have been used as molten protic media to promote isotopic exchange reactions. Ammonium sulphate, diammonium hydrogen ortho-phosphate and ammonium chloride were used as catalysts which provide acidic media to facilitate exchange reactions. Maximum radiochemical yields of 97.1±1.3% and 84.3±1.6% [131I] MIBG were obtained when ammonium sulphate and benzoic acid were used. High radiochemical yields of 88.3±1.1% and 74.4±1.5% [131I] MIBG were also obtained in case of diammonium hydrogen orthophosphate and pivalic acid which suggests their successful use as reaction media in the radioiodination of MIBG. The activation energy for the exchange reaction in ammonium sulphate was calculated to be 10.8 kcal/mole.

Preparation of radioiodinated L-α-methyl tyrosine, a tumour brain imaging agent

Preparation of radioidinated L-α-methyl tyrosine by the oxidative radioiodination using chloramine-T (CAT) and iodogen (1,3,4,6-tetrachloro,-3α, 6α-diphenyl glycoluril) to generate electrophilic radioiodine has been carried out. The factors affecting the labeling yield such as pH of the medium, reaction time, substrate and oxidizing agent concentrations have been investigated to optimize the conditions for the preparation of radioiodinated L-α-methyl tyrosine in high radiochemical yields. Side product impurities were observed at long reaction times and high oxidizing agent concentrations. Maximum radiochemical yields of 89.7±1.5% and 87.8±1.6% were obtained in case of CAT and iodogen, respectively. Separation and purification by high pressure liquid chromatography (HPLC) resulted in radiochemically pure products. Using high specific activity123I, the SPECT brain imaging agent can be prepared.

Regioselective radiofluorodestannylation with [ 18F]F 2 and [ 18F]CH 3COOF: A high yield synthesis of 6-[ 18F]fluoro- l-dopa

A protected 6-trimethylstannyl dopa derivative 6 has been synthesized for the first time as a precursor for the preparation of 6-[ 18F]fluoro- l-dopa. The tin derivative 6 readily reacted with electrophilic radiofluorinating agents such as [ 18F]F 2 and [ 18F]AcOF. The [ 18F]fluoro intermediate 7 was easily hydrolyzed with HBr and the product 6-[ 18F]fluoro- l-dopa was isolated after HPLC purification in a maximum radiochemical yield of 25%, ready for human use. The various intermediates, the stannyl precursor 6 and the final product (after 18F decay) were all fully characterized by 1H, 13C, 19F and 119Sn NMR as well as high resolution mass spectroscopy.

Synthesis of NO‐carrier added 11C‐labelled [methyl]choline analogs

AbstractWe describe here the synthesis of two[11C‐methyl]labelled analogs of choline and the influence of the solvent, addition of a base, and reaction time on the radiochemical yield. The reactions produced equally good yields in methanol and acetonitrile and reached maximum radiochemical yield at about 5‐10 min. The addition of a base in the case of [11C‐methyl]pyrrolidinocholine increases the radiochemical yield. Optimum radiochemical yields were 30% for[11C‐methyl]piperidinocholine and 40% for[11C‐methyl]pyrrolidinocholine for two choline analogs.

Synthesis, quality control and tissue distribution of 2-[18F]-nicotinic acid diethylamide, a potential agent for regional cerebral function studies

2-[18F]-nicotinic acid diethylamide was prepared by nucleophilic aromatic substitution in an acetamide melt of the corresponding chloro-compound and purified by high pressure liquid chromatography. Optimization of the reaction conditions led to a maximum radiochemical yield of about 50% within less than one half-life of18F. Tissue distribution of 2-[18F]-nicotinic acid diethylamide in various organs of mice showed a very fast accumulation of activity in the brain (mean body concentration MBC-239%) with a brain to blood ratio of 1.34.

Chloramine‐t for “no‐carrier‐added” labelling of aromatic biomolecules with bromine‐75,77

AbstractThe applicability of chloramine‐T (CAT) was examined for “no‐carrier‐added” labelling of aromatic compounds with the short‐lived isotopes bromine‐77 (T1/2 = 56 h) and bromine‐75 (T1/2 = 98 min). In aqueous solution the optimum reaction conditions with respect to pH, concentration of CAT, reaction time and added brominecarrier were determined using tyrosine as a model substrate. Highest radiochemical yields (>85%) were obtained at pH 1 within a few seconds at a CAT concentration of 10−3 M. At pH 7 a maximum radiochemical yield of 65% was achieved with 10−2 M after 2.5 minutes. Studies with some model peptides showed that only the tyrosyl residues were brominated and similar yields were obtained as in free tyrosine. Some aromatic molecules such as α‐methyl‐tyrosine, phenylalanine, uracil, cytosine, and phenol were radiobrominated by the CAT method with yields up to 90%. Separation and identification of the labelled products were achieved by means of radio high performance liquid chromatography.

Synthesis, chromatography and tissue distribution of 1‐[11 C]‐hexobarbital

Abstract1‐[11C]‐Hexobarbital was synthetized by methylation of norhexobarbital using 11CH3I. The maximum radiochemical yield after purification by hplc is 47% at a specific activity of 1.0 mCi/μmole. Synthesis time including purification is 37 min. The tissue distribution was determined in mice at different times after i.v. injection. The main accumulation of activity during the first hour after i.v. injection is in liver and kidneys. Other well perfused organs like brain, heart and lung show significant accumulation only during the first minutes after injection.

A Study of the Recoil Labeling of Fluothane with 82Br during Neutron Irradiation

Abstract 1,1,1-Trifluoro-2-chloro-2-bromoethane labeled with 82Br (fluothane-82Br) was purely separated from neutron-irradiated fluothane by means of a gas-chromatographic technique. The maximum radiochemical yield of fluothane-82Br was 38.3% when the target material was irradiated with neutrons to nvt of 3.4×1016 n·cm−2. Of the many organic species produced by the recoil events following the radiative neutron capture and subsequent (I.T.) processes, CF382Br and CF3CHBr82Br were also identified. In order to elucidate the mechanism of recoil labeling, the scavenger effects were examined in the CF3CHClBr–Br2 system, Br2 being used as a radical scavenger. The “high-energy” yields of CF3CHCl82Br thus estimated were approximately 3.6 to 4.8%. It was suggested that most of the 82Br-labeled species were formed through the “thermal” processes including the reaction of 82Br with the organic radicals produced by the radiolysis of the parent fluothane.

Synthesis of high specific activity C 14-carboxyl indoleacetic acid and of C 14-nitrile indoleacetonitrile

Existing methods which can be modified for the synthesis of C 14 carboxyl-labeled indoleacetic acid have been surveyed and the conditions necessary to obtain the maximum radiochemical yield from C 14-cyanide were determined. A major problem is the autoradiosensitivity of the product, which can be minimized by storage in dilute acetonitrile solution. Detailed procedures are given for a convenient one-day synthetic method for high purity indoleacetic acid and indoleacetonitrile. The former has been prepared with specific activities up to 16.9 mc/mmole. At the highest specific activity levels, autoradiodecomposition during the course of synthesis apparently limits the yield obtained.