Isotope exchange of iodine between sodium iodide [Na131I] and [4-127I]iodoantipyrine via organic medium

The present investigation deals with a study of the isotope exchange reaction of iodine between sodium iodide [Na¹³¹I] and [4-¹²⁷I]iodoantipyrine in organic medium, using different iodinating radioiodine reagents of different carrier-iodine concentration. A maximum saturation yield over 90% of pure [4-¹³¹I]iodoantipyrine has been obtained by performing the isotope exchange reaction in ethanol at 80°C in 30 min. The same yield has been obtained using the same concentrations by performing the reaction at room temperature (17–20°C) for 3 h. Also the rate of the isotope exchange reaction was found to be carrier-iodine dependent as well as time and temperature dependent. According to these results and reaction conditions, a kit form method was elaborated for the synthesis of [4-¹³¹I]iodoantipyrine as well as [4-¹²³I]iodoantipyrine.     

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.     

Fast high yield labelling of 16-Br-hexadecanoic acid with radioactive iodine using quaternary ammonium salts

The catalytic effect of quatemary ammonium ion on the reaction between 16-bromohexadecanoic acid (16-BrHDA) with Na¹³¹I in two phase system has been detemined. The technique described here is based on nonisotopic exchange reaction between 16-BrHDA and Na¹³¹I using phase transfer catalysis. Four quaternary ammonium salts (as phase transfer catalyst PTC) and one crown ether were examined. The kinetics are linearly dependent on catalyst content, offering radiochemical yield of more than 90% within 10 minutes at 60 °C. The effect of different temperatures on the radiochemical yield of 16-¹³¹IHDA have been studied to determine the activation energies of the exchange processes between 16-BrHDA and Na¹³¹I. In the presence of PTC, the activation energies of 8.3–9.7 kcal/mol were determined. Also in dry state and in absence of PTC the activation energy was measured and found to be 21.95 kcal/mol.     

A modified method for no carrier added radioiodination of L-tyrosine via chloramine-T as an oxidizing agent

A modified method for the preparation of L-[^131/123I] iodotyrosine as a brain imaging agent is described. The method is based on direct electrophilic radioiodination of L-tyrosine with NaI [^131/123I] using chloramine-T (CAT) and 0.001 g KI as a carrier at pH 7.0. The product was purified by reverse phase high performance liquid chromatography (HPLC). A high radiochemical yield up to 85% of L-[^131/123I] iodotyrosine has been achieved with radiochemical purity of greater than 97%. The relation between the pKa of L-tyrosine and pH of the reaction medium was calculated in order to correlate the radiochemical yield of L-[^131/123I] iodotyrosine and the state of the three ionizable groups of L-tyrosine. Also, the influence of the reaction conditions on the radiochemical yield of L-[^131/123I] iodotyrosine was investigated.     

Nucleophilic radioiodination of 6-bromocholesterol via non-isotopic exchange reaction in molten state

A synthetic method for preparing radioiodinated 6-[125 I]iodocholesterol[CL-6-125 I] for adrenal evaluation is described. The radioiodine atom wasincorporated onto the cholesterol molecule via non-isotopic exchange between6-bromocholesterol [CL-6-Br] and radioiodine as iodide ion [ 125 I –]in a molten state. The different parameters affecting the yield of exchange were investigated using 125 I (T 1/2 .60 d) to centralize the different physical and chemical reaction conditions and purification of the final product as pure as 6-[125 I]iodocholesterol. The method was suitable to either 131 I (T 1/2 .8 d) nucleophilic radioiodination which facilitates the scanning of the adrenal for a few days after administration or the use of 124 I (T 1/2 .4.16 d) nucleophilic radioiodination for PET evaluation of the adrenal. TLC as well as HPLC chromatographic analysis is used to determine the efficiency of the exchange reactions under different chemical reaction conditions and to monitor the stability of the final product as pure as CL-6-125 I with radiochemical purity of .99%. This no-carrier-added method improved the speed of the reaction and affords high radiochemical yield of 90 % and suitable specific activity due to the use of CL-6-Br rather than CL-6-I as substrate. Kinetic studies revealed second order iodine-bromine exchange reaction. The activation energy for the exchange reaction in ammonium acetate (m.p. 114 °C) was calculated to be 4.576 kcal/mole.     

Astatine-211 labelled proteins and their stability in vivo

In an ongoing effort to obtain quantitative, rapid kit type labelling of [¹²³I] radiopharmaceuticals, we have examined organomercury precursors of [¹²³I] 15-(para-iodophenyl)-pentadecanoic acid (IPPA). Chloromercuri derivatives of phenyl pentadecanoic acid (PPA) and the PPA ethyl ester were obtained by mercuration utilizing mercuric trifluoroacetate in trifluoroacetic acid followed by treatment with acetic acid and hydrochloric acid. The most simple compound, chloromercuri PPA, proved insoluble at room temperature in the common solvents useful for radioiodination and purification. The study was extended in a systematic way to chloromercuri PPA ethyl ester and the acetoxy mercuri PPA ethyl ester. As expected, these two compounds posessed successively more useful ranges of solvent compatibility. Iodination and [¹²³I] radioiodination were carried out with the three compounds of PPA. Chloromercuri PPA was dissolved with difficulty in acetic acid at 70°C and 71% radiochemical yield of [¹²³I] IPPA was obtained during the course of a 5 minute reaction utilizing chloramine T. The chloromercuri PPA ethyl ester was dissolved in ethyl acetate/acetic acid (2/1 v/v) at room temperature and 87% radiochemical yield of [¹²³I] IPPA was obtained following 10 minutes reaction. With the acetoxy mercuri PPA ethyl ester it was possible to conduct the radioiodination in ethanol again using chloramine T. A modest radiochemical yield (r. y.) (51%) of [¹²³I] IPPA ethyl ester was obtained after 60 min. It was possible to enhance the radiochemical yield in the presence of lithium acetate (84% r. y.). The isomeric purity of the [¹²³I] IPPA ethyl ester was unexpectedly high (99.9% para) when the radioiodination was conducted at room temperature.     

N-[11C]methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB): synthesis, quality control and biodistribution

N-[¹¹C]methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine ([¹¹C]MBDB) 3 was prepared by methylation of the demethyl precursor BDB with [¹¹C]CHI. The radiosynthesis was optimized with regard to temperature, reaction time and amount of precursor, best results (i.e., 84% radiochemical yield, based on [¹¹C]CH₃I activity) were obtained using 3 mg BDB at a reaction temperature of 130 °C in 8 minutes. With respect to a facilitated workup routine, productions were performed with 0.6 mg BDB at 110 °C for 10 minutes, yielding more than 50% of 3. The radiochemical purity of the final tracer solution was >98%, the specific activity was determined to be 300 GBq/mol (8000 Ci/mmol). Biodistribution, studies in rats showed two major metabolic pathways as indicated by an increasing liver uptake (9.1% ID/organ at 5 minutes to 21% ID/organ at 30 minutes) and a high urine activity (up to 16% ID/g). In brain tracer uptake was more than 1%, with a brain to blood ratio of almost 12 resulting from a very rapid blood clearance of 3.     

Radioiodination of 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine, 4-(3-iodobenzyl)-1-(benzylsulfonyl)piperazine and their derivatives via isotopic and non-isotopic exchange reactions

A mild and simple technique for preparing of 4-benzyl-1-(3-[¹²⁵I]iodobenzylsulfonyl)piperidine, 4-(3-[¹²⁵I]iodobenzyl)-1-(benzylsulfonyl)piperazine and their derivatives, as sigma-1 receptor ligands, with relatively high radiochemical yields via nucleophilic substitution reaction by means of isotopic and non-isotopic exchange reactions is described. Some factors affecting the radiochemical yield were commonly studied in presence of acidic medium at elevated temperature. Unfortunately, the radiochemical yields were weak. Some attempts were carried out in presence of polar aprotic solvents to enhance the radiochemical yield. N,N-Dimethylformamide was proved highly efficient for preparing of radioiodinated 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine (4-B-[¹²⁵I]-IBSP, 70 ± 5.7 %) and 4-(3-iodobenzyl)-1-(benzylsulfonyl)piperazine (4-[¹²⁵I]-IBBSPz, 72 ± 6.0 %) at moderate temperature (100–105 °C) within 8 h. The specific activities of 4-B-[¹²⁵I]-IBSP and 4-[¹²⁵I]-IBBSPz (6,534.2 and 5,927.4 MBq/mmol) were obtained respectively.     

Chemical and thermodynamic characteristics of the isotopic exchange reaction between radioiodine and iodohippuric acid isomers.

The parameters affecting the absolute radiochemical yield of the isotopic exchange reaction between radioiodine (125I-) and iodohippuric acid isomers on molten ammonium acetate as a medium exchange at 120 degrees C without any carrier added (radioiodine, 125I-) was determined. The isotopic exchange reactions of radioiodine as 125I- for iodine-127 of o- and p-iodohippuric acid isomers occur more rapidly than m-iodohippuric acid isomer. These reactions proceed by nucleophilic second order substitution reaction. The kinetics and thermodynamic parameters of these isotopic exchange reactions were determined. The absolute radiochemical yield and radio pharmaceutical purity were determined by HPLC and TLC techniques.     

Preparation of high purity labelled Rose-Bengal with radioiodine

The exchange of Rose-Bengal in the mono-sodium salt with elementary¹³¹I in an organic medium allows for the preparation of a labelled product substantially higher in radiochemical purity than that produced by other methods. Purification of the starting material before the labelling process has been done by adsorption chromatography. Under the conditions described a radiochemical yield more than 97% can be obtained within 30–60 minutes. The product was stable during sterilization and storage for 10 days and was found to be free of¹³¹I.     

Preparation of N-[11C]methyl-2,5-dimethoxy-4-methylamphetamine

In order to evaluate the neurobiological mechanism causing the psychogenic effects of N-methyl-2,5-dimethoxy-4-methylamphetamine (MDOM), the¹¹C labelled analogue was prepared for application in in vivo PET studies by the reaction of 2,5-dimethoxy-4-methylamphetamine (DOM) with [¹¹C]CH₃I. The radiochemical yield was determined in dependence on time, temperature, solvent and amount of substrate. The best conditions for fast labelling reactions with¹¹C on a preparative scale were found to be a reaction time of 10 miutes at 110°C using 1 mg DOM in acetonitrile thus obtaining radiochemical yields of 80% (based on produced [¹¹C]CH₃I).     

Separation of131I by isotopic and non-isotopic liquid ion exchange

A study is presented on the use of isotopic and non-isotopic ion exchange in a heterogeneous liquid-liquid system for the separation of¹³¹I from water. The method is based on the reaction between radioiodide in the aqueous phase and trioctylmethylammonium iodide or chloride in the organic phase. The effect of some important experimental parameters on the separation efficiency is discussed. It has been found that under optimum conditions the method of isotopic ion exchange can be used for the radiochemical determination of iodine in water.     

Preparation of Iodine-131 Labeled Hippuran by Exchange Method

I^131?labeled Hippuran was prepared by isotopic exchange reaction between ortho-iodohippuric acid and I¹³¹-iodide. Special emphasis was placed on the separation of I^131?labeled Hippuran and its analysis with respect to the radiochemical purity. It was found that the prepared I¹³¹-labeled Hippuran meets the requirement as the radiopharmaceutical to be used for medical purpose.     

Preparation of 1-Phenyl 3-Methyl 4-Nitro 5-125I- Pyrazole (5-125I-MNPP) as a Possible Cannabinoid Receptor Imaging Agent

A rapid method for labelling of 1-phenyl 3-methyl 4-nitro 5-chloro pyrazole (5-Cl-MNPP) with radioactive iodide Na¹²⁵I via ¹²⁵I -for- Cl exchange has been reported. This method has been done in dry state (without catalyst and in presence of acetamide), in dimethyl formamide (DMF) as a solvent (without catalyst and in presence of tetrabutyl ammonium bromide (TBAB) as phase transfer catalyst (PTC)). In dry state, a trial to reduce the reaction temperature from 170 to 120 °C for the reaction between 5-Cl-MNPP and Na¹²⁵I in presence of acetamide as a molten medium was tested. Using some organic solvents such as ethanol, dimethyl sulfoxide (DMSO), acetonitrile, and DMF, it was found that DMF gave low radiochemical yield of 5-¹²⁵I-MNPP (25%) within 30 min. However, the addition of 1 mg of TBAB to DMF increased the radiochemical yield of 5-¹²⁵I-MNPP from 25 to 95 within 30 minutes. The product 5-¹²⁵I-MNPP was purified by reverse phase, high performance liquid chromatography (HPLC), with radiochemical purity of greater than 98.0%. The biodistribution of 5-¹²⁵I-MNPP was demonstrated in normal mice through intravenous injection in the tail vein. The data show high uptake in the target organs equal to 2.5±0.22, 10.5±0.21, 4.3±0.27, 3.2±0.18 and 48.5±0.26 for brain, intestines, heart, kidneys and liver respectively. This indicates that, 5-¹²⁵I-MNPP can be freely penetrate the blood brain barrier (B.B.B.) and can be expected its usefulness in the quantitative determination of cannabinoid receptor in the brain.     

Synthesis and preliminary biodistribution studies of [<Superscript>131</Superscript>I]SIB-PEG<Subscript>4</Subscript>-CHC in tumor-bearing mice

This work reports the synthesis and preliminary biodistribution results of [¹³¹I]SIB-PEG₄-CHC in tumor-bearing mice. The tributylstannyl precursor ATE-PEG₄-CHC was synthesized by conjugation of ATE to amino pegylated colchicine NH₂-PEG₄-CHC. [¹³¹I]SIB-PEG₄-CHC was radiosynthesized by electrophilic destannylation of the precursor with a yield of ~44%. The radiochemical purity (RCP) appeared to be >95% by a Sep-Pak cartridge purification. [¹³¹I]SIB-PEG₄-CHC was lipophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that [¹³¹I]SIB-PEG₄-CHC cleared from background rapidly, and didn’t deiodinate in vivo. However, the poor tumor localization excluded it from further investigations as a tumor-targeted radiopharmaceuticals.     

A facile preparation of ammonium [<Superscript>14</Superscript>C]thiocyanate

Summary An attractive and simple method has been developed for the preparation of ammonium [¹⁴C]thiocyanate from [¹⁴C]thiourea which eliminates the necessity of handling highly hazardous potassium [¹⁴C] cyanide. [¹⁴C]thiourea was isomerized to ammonium [¹⁴C]thiocyanate by heating the aqueous solution of thiourea (12%) in a sealed tube at 160 °C for 24 hours. The product formed was purified by silica-gel column chromatography. A radiochemical yield of 92.7% was obtained based on [¹⁴C]thiourea. The specific activity of the product obtained was 53.3 mCi/mmol (1.97 GBq/mmol) and the radiochemical purity was greater than 99%. This method has not been reported so far for the production of this labeled compound.     

Comparative study between chloramine-T and iodogen to prepare radioiodinated etodolac for inflammation imaging

This study describes a fast and efficient method for radiolabeling of etodolac with iodine-125 [¹²⁵I], where both chloramine-T and iodogen were used as oxidizing agents. The labeling reaction was carried out via electrophilic substitution of hydrogen atom with the iodonium cation I⁺. The labeling yield was found to be influenced by different factors such as drug concentration, pH of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media. The radiochemical yield (RCY) was determined by TLC system using methylene chloride:ethyl acetate (3:7 v/v) as a developing solvent and by electrophoresis using cellulose acetate moistened with 0.02 M phosphate buffer pH 7. The maximum radiochemical yield of [¹²⁵I]Etodolac (87.7%) was obtained. Labeled etodolac shows a good localization in inflamed muscle. It excretes mainly via kidney and to some via liver.     

Preparation of N-[11C]methyl-2,5-dimethoxy-4-bromo-amphetamine

For in vivo receptor studies N-[¹¹C]methyl-2,5-dimethoxy-4-bromo-amphetamine, [¹¹C]MDOB, was synthesized by the reaction of [¹¹C]CH₃I with DOB in acetonitrile. The labelling yield was determined in dependence on amount of precursor, time and temperature of the methylation reaction. During 10 to 15 minutes 60% to 70% of [¹¹C]MDOB has been obtained at 110°C.     

Kinetics of isotope exchange between [3-(iodophenyl)methyl]guanidine (mIBG) and [131I]-iodide

The reaction of isotope exchange between [3-(iodophenyl)methyl]guanidine, mIBG, and [¹³¹]-iodide in relatively concentrated solutions, in the presence of different ammonium salts, in a closed system, over the temperature range from 130 to 150°C, has been investigated. The reaction occurs either with (NH₄)₂SO₄ or CH₃COOH, which indicates that the reaction goes through some intermediate stages. Kinetic studies show the influence of the additives. The activation energies for the reaction with (NH₄)₂SO₄/H₂O, (NH₄)₂SO₄/CH₃COOH and CH₃COOH are 121.1, 115.1 and 84.5 kJ·mol^–1, respectively.     

Automated synthesis of hypoxia imaging agent [18F]FMISO based upon a modified Explora FDG4 module

A new automated synthesis procedure of 1-H-1-(3-[¹⁸F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([¹⁸F]FMISO), a specific hypoxia imaging agent with great significances for the noninvasive, dynamic hypoxia evaluation of cancer, was developed by modifying Explora FDG₄ module, a commercial [¹⁸F]FDG production system, in this study. Its radiochemical synthesis was carried out via two sequent reaction steps, i.e. the nucleophilic displacement of labeling precursor 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-tosyl-propanediol (NITTP) with activated ¹⁸F- ion at 100 °C for 8 minutes, and the following hydrolysis with 1M HCl at 100 °C for 5 minutes and neutralization with 1M NaOH. Two-pot reaction with two independent separations was adopted to assure the good separation of final product via solid phase extraction (SPE) based upon combined Sep-pak cartridges instead of high performance liquid chromatography (HPLC). This fast, reliable preparation route of ¹⁸F-FMISO could complete within 50 minutes with about 55% of high radiochemical yield (with decay correction) and more than 98% of good radiochemical purity. The modified module could perform multiple runs of production of [¹⁸F]FMISO.