Optimization of the preparation conditions of radioiodoepidepride: A dopamine D<Subscript>2</Subscript>receptor antagonist radioligand

Summary [¹²⁵I]iodepidepride, (s)-(-)-[(1-ethyl-2-pyrrolidinyl)methyl]-5-[¹²⁵I]-iodo-2,3-dimethoxybenzamide is the iodine substituted analogue of isoremoxipride, both of which are very potent dopamine D₂-antagonists. Epidepride was radioiodinated using different oxidizing agents such as chloramine-T, iodogen, iodogen glass frit and hydrogen peroxide. Chloramine-T is a powerful oxidizing agent compared to both iodogen and hydrogen peroxide so that the side products, especially the chlorinated epidepride, decreases the radiochemical yield. This chlorinated epidepride is minimized in the case of iodogen and iodogen glass frit and are not observed in case of the non-chlorinated oxidizing agent hydrogen peroxide. TLC and HPLC were used to analyze the reaction components and to estimate both the radiochemical yield and purity. The reaction parameters such as reaction time, pH, epidepride and oxidizing agent concentrations and the stabilty of the final product were studied to optimize the radiochemical yield and purity. The optimized radiochemical yield was about 90% and the radiochemical purity of the final product was 99.9%.     

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.     

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 <Superscript>125</Superscript>I-celecoxib with high purity as a possible tumor agent

A preparation of ¹²⁵I-celecoxib is carried out via an electrophilic substitution reaction. The reaction parameters studied were celecoxib concentration, reaction temperature, pH of the reaction mixture and kinds of oxidizing agents in order to obtain a high radiochemical yield of the ¹²⁵I-celecoxib. Using 3.7 MBq of Na¹²⁵I, 150 μg (3.9 mM (mmol/L)) of celecoxib, and 1.6 mM (mmol/L) of chloramine-T (CAT) as oxidant at pH 4 and 60 °C for 15 min a maximum radiochemical yield of ¹²⁵I-celecoxib (65%) was obtained. The labeled compound was separated and purified by means of high pressure liquid chromatography (HPLC). The biological distribution in infected mice indicates the suitability of radioiodinated celecoxib as imaging of tumor.     

Fast Efficient Method for Radiolabeling of Pindolol with Iodine-125 Using Iodogen Coated Glass Frit

Although ¹²⁵I-hydroxypindolol (¹²⁵I-HYP) has been an excellent probe of adenoceptor function in certain tissues, but ¹²⁵I-pindolol (¹²⁵I-PIN) was found more specific for -adrenoceptor labeling. This study describes a fast and efficient method for radiolabeling of pindolol with iodine-125, where both chloramine-T and iodogen were used as oxidizing agents. The use of iodogen coated glass frit has a great advantage in increasing the radiochemical yield of ¹²⁵I-pindolol and this was attributed to the increase of the interphaces boundary between the solid and liquid. This technique reduces the quantity of iodogen required to produce high radiochemical yield by its half. The radiochemical yield was determined by TLC system using chloroform: acetic acid: water (15:4:1) as developing solvent and by HPLC using reversed phase RP-18 column and acetonitrile: 0.1M ammonium bicarbonate pH 7.5 (1:1) as a mobile phase at flow rate (1ml/min). The radiochemical yield was found to be 48.6 and 62.9% respectively.     

Preparation of radioiodinated khellin for the urinary tract imaging

Khellin, 4,9-dimethoxy-7-methyl-5H-furo[3,2-g]chromen-5-one, the most biologically active furochromone present in Ammi visnaga fruits indigenous to Egypt. A procedure for radioiodination of khellin with ¹²⁵I is carried out via an electrophilic substitution reaction. The reaction parameters studied were khellin amount, pH of the reaction mixture, reaction time, temperature, different oxidizing agents and different organic media to optimize the conditions for the labeling of khellin and to obtain a high radiochemical yield of the ¹²⁵I-khellin (¹²⁵I-Khel). Using 3.7 MBq of Na¹²⁵I, 100 μg (0.96 mM) of khellin as substrate, 100 μg (1 mM) of chloramine-T as oxidizing agent in ethanol at 60 °C for 10 min, a maximum radiochemical yield of ¹²⁵I-Khel (78 %) was obtained. The specific activity of ¹²⁵I-Khel was 3 MBq/0.5 mM. The biological distribution in normal mice indicates that radioiodinated khellin is a novel agent for urinary tract infection imaging.     

Radioiodination of C60 Derivative C60(OH)xOy

In this paper water-soluble fullerene derivative C₆₀(OH)_xO_y was radioiodinated with the iodogen method. The labeling yield was determined by radio-TLC. The effects of pH value, reaction time, temperature and amount of the iodogen on the labeling yield were studied. The labeled product was purified by Sephadex G-25 column chromatography and then the stability of ¹²⁵I-C₆₀(OH)_xO_y was examined . The results showed that the radiochemical purity of ¹²⁵I-C₆₀(OH)_xO_y solution with benzylalcohol remained 82.7% after 43 hours.     

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.     

Labeling of atenolol with radioactive iodine-125 using <Emphasis Type="Italic">N</Emphasis>-bromosuccinimide and hydrogen peroxide as oxidizing agents

An adopted method for the preparation of high radiochemical purity ¹²⁵I-atenolol was investigated. Direct radioiodination of atenolol was carried out using N-bromosuccinamide or hydrogen peroxide as an oxidizing agent. The reaction proceeds well within 30 min at room temperature (25 ± 1 °C) and afforded a radiochemical yield up to 97% as pure as ¹²⁵I-atenolol. Different chromatographic techniques (electrophoresis, TLC and HPLC) were used to determine the radiochemical yield and purity of the labeled product. Biodistribution studies were carried out in normal Albino Swiss mice and the results indicate that ¹²⁵I-atenolol can be used safely as myocardial imaging agent.     

Potential diagnostic and therapeutic agents for malignant melanoma: Synthesis of heavy radiohalogenated derivatives of methylene blue by electrophilic and nucleophilic methods

Heavy radiohalogenated derivatives of methylene blue of potential value as possible diagnostic and endoradiotherapeutic agents for malignant melanoma, have been synthesized by both electrophilic and nucleophilic reaction routes. Thermal halogen isotope exchange in molten crown ether catalyst facilitated the rapid preparation of high specific activity radioiodinated and [²¹¹At]-astatinated derivatives; radiochemical yields were in the order of 60–79%. Radiohalogenation mediated by chloramine-T or via diazonium intermediary proved more laborious, far less efficient and inappropriately is only suited to the preparation of low specific activity product.     

Separation of <Superscript>125</Superscript>IBZM and <Superscript>125</Superscript>ILIS using polyacrylamide-acrylic acid resin

Radioiodination of both S(−)BZM and LIS was carried out using n-bromosuccimide(NBS) as a mild oxidizing agent. The factors affecting on the radiochemical yield such as pH, reaction time, substrate concentration and oxidizing agent have been studied. The chromatographic separation of both ¹²⁵IBZM and ¹²⁵ILIS was carried out using HPLC and poly(acrylamide-acrylic acid) resin P(AAm-AA). The copolymer was prepared by a template polymerization of AA in aqueous solution on PAAm as a template polymer and in the presence of N,N-methylenebisacrylamide (NMBA) as a crosslinker using gamma rays as initiator. The purifications of tracers were carried out using prepared resin compared with TLC and HPLC. The effects of pH buffer, variable elution volumes, flow rate and temperature on the separation process of the resin efficiency have been studied.     

Chlorination as a side reaction in radioiodination with chloramine-T

Chloramine-T is often used as an oxidizing agent for radioiodide in the electrophilic labeling of proteins and phenolic compounds. We have found that chloramine-T is also capable of introducing chlorine under the right conditions. Thus, treatment of fluorescein with no-carrier added¹²⁵I-sodium iodide and chloramine-T resulted in a uv-absorbing, fluorescent product in addition to the (no-carrier-added)¹²⁵I labeled material. The by product was tentatively identified as a chlorinated fluorescein by comparison with a known sample. The potential of macrochlorination should be kept in mind when using chloramine-T for radioiodination.     

Kinetics and mechanism of oxidation of dimethyl sulfoxide by chloramine-T in aqueous solution

The kinetics of oxidation of dimethyl sulfoxide (DMSO) by chloramine-T (CAT) is studied in HClO₄ and NaOH media with OsO₄ as a catalyst in the latter medium. In acid medium, the rate law is -d [CAT]/dt = k [CAT][DMSO][H⁺]. Alkali retards the reaction and the rate law takes the form -d [CAT]/dt = k [CAT][DMSO][OsO₄]/[NaOH], but is reduced to -d [CAT]/dt = k [CAT][DMSO] at higher alkali concentrations. The reaction is subjected to changes in (a) ionic strength, (b) concentrations of added neutral salts, (c) concentrations of added reaction product, (d) dielectric constant, and (e) solvent isotope effect, and the subsequent effects on the reaction rate are studied. The reaction mechanism in acid medium assumes an electrophilic attack by the free acid RNHCl (CAT′) at the sulfur site in DMSO, forming a reaction intermediate which subsequently decomposes to dimethyl sulfone on hydrolysis. Formation of a cyclic complex between RNHCl and OsO₄ which interacts with the substrate in a slow step explains the observed results in alkaline medium. The simplification of the rate equation at higher alkali concentrations is attributed to a direct reaction between chloramine-T and the substrate.     

Preparation of 125I-cytarabine and its radiochemical evaluation: Model of radio-therapeutic agent

This paper adresses the development of a new radiopharmaceutical for cancer imaging and therapy. The optimization of the labeling of thymidine analogous, cytarabine, with ¹²⁵I is described. High radiochemical yield and purity 98% was obtained by reacting 50 mg cytarabine with ¹²⁵I in the presence of iodogen as oxidizing agent and 0.5M phosphate buffer of pH 7 at 65 °C for 30 minutes. Preliminary in-vivo study was done in non-tumor bearing mice. The results revealed that this new tracer, ¹²⁵I-cytarabine, has a high affinity to be localized in tissues of high proliferation rate, e.g., bone marrow 10%, 60-minute post administration. Also, the labeled compound was cleared quickly from most of the body organs and concentrated in bladder 55%, 60-minute post administration. These findings suggest that ¹²⁵I-cytarabine, allows imaging and treatment of cancer. ¹²⁵I-cytarabine meets most of the requirements to be used as a successful diagnostic and therapeutic agent: it is a low molecular weight molecule that diffuses readily in tissues, it will not induce an antibody response, thereby leading itself to repeated injection or continuous infusion.     

Study on labeling conditions of125I-synkavit by the iodogen method

Labeling conditions of synkavit (2-methyl-1,4-naphthoquinol disodium phosphate) with iodine-125 have been studied. In this study, labeling temperature, reaction time, successive using of iodogen coated tubes, iodogen amount and synkavit concentrations have been determined to get optimum conditions for maximum labeling. Final results showed that when the labeling temperature, reaction time, synkavit concentration, and iodogen amount were, at room temperature, 15 min (in the case of successive using of three iodogen coated tubes), 2 mg ml^–1 and 5 mg, respectively; labeling yield was 90% and specific activities of the order of 555 GBq mmol^–1 (15 Ci mmol^–1) have been obtained.     

Pulse radiolysis study of dithio-oxamide in aqueous solutions

The reactions of e⁻ _aq, H-atoms, OH radicals and some one electron oxidants and reductants were studied with dithio-oxamide (DTO) in aqueous solutions using pulse radiolysis technique. The transient species formed by the reaction of e⁻ _aq with DTO at pH 6.8 has an absorption band with λ _max at 380 nm and is reducing in nature. H-atom reaction with DTO at pH 6.8 also produced the same transient species. The semi-reduced species was found to be neutral indicating that the electron adduct gets protonated quickly. However at pH 1, the species produced by H-atom reaction had a different spectrum with λ _max at 360 and 520 nm. Reaction of acetone ketyl radicals and CO₂ ⁻ radicals with DTO at pH 6.8 gave transient spectra which were identical to that obtained by e⁻ _aq reaction. However at pH 1, the spectrum obtained by the reaction of acetone ketyl radicals with DTO was similar to that obtained by H-atom reaction at that pH. The transient species formed by OH radical reaction with DTO in the pH range 1–9.2 also has two absorption maxima at 360 and 520 nm. This spectrum was identical with the spectrum obtained by H-atom reaction at pH 1. This means that all these radicals viz. OH, H-atom and (CH₃)₂COH radicals react with DTO at pH 1 by H-abstraction mechanism. The transient species produced was found to be sensitive to the presence of oxygen. One-electron oxidizing radicals such as Br₂ ^−· and SO₄ ^−· radicals reacted with DTO at neutral pH to give the same species as produced by OH radical reaction having absorption maxima at 360 to 520 nm. At acidic pHs, only Br₂ ^−· and Cl₂ ^−· radicals were able to oxidize DTO to give the same species as produced by OH radical reaction. The semioxidized species is a resonance stabilized species with the electron delocalized over the-N-C-S bond. This species was found to be neutral and non-oxidizing in nature.     

Radiolabeling of EGCG with 125I and its biodistribution in mice

The aim of the present study was to label EGCG with ¹²⁵I and to determine its radiopharmaceutical potential in mice. EGCG was labeled with ¹²⁵I using the iodogen method. The labeling yield and the radiochemical purity of ¹²⁵I–EGCG were determined by radio thin-layer chromatography (RTLC). The Labeling yield was approximately 89.4 %. The radiochemical purity was approximately 96.4 %. The biodistribution studies of the labeled compound (specific activity; 0.47 TBq/μg) were performed in male Kunming mice. The uptakes of ¹²⁵I–EGCG in some organs were determined at different time after injection to the mice. The radioactivity in each organ was counted and the percentage of injected activity per gram of tissue weight (%ID/g) for each organ and blood was calculated. Incorporation of radioactivity in the various tissue/organ was confirmed by microautoradiography. ¹²⁵I–EGCG uptake in the stomach and salivary gland was higher than other organ/tissue. The black silver grains was concentrated in the nucleus, cytoplasm, intercellular substance and capillaries of that various organs, and its unevenly distributed. Thus, ¹²⁵I–EGCG may be radiopharmaceutical for the imaging of the stomach and salivary gland.     

Comparison study between direct and indirect labeling of estradiol for radioimmunoassay purpose

In the present study, estradiol (E₂) which contains an aromatic phenol ring in its chemical structure was chosen for direct and indirect labeling techniques using ¹²⁵I and chloramine-T oxidation method. In direct technique the hydrogen atom in phenol ring was replaced by a radioiodine atom directly, which in indirect one, histidine methyl ester (HME) was labeled firstly with ¹²⁵I using chloramine-T method then conjugated with E₂. The ¹²⁵I-labeled materials were purified using HPLC technique. The comparison study between the two obtained tracers was carried out in terms of radiochemical purity, binding percent, specific activity, non specific binding, binding displacement, shelf life using a radioimmunoassay (RIA) with specific antibody. The results indicated that indirect iodination of estradiol will cause significant increasing in studied parameters when combined with specific antibody than direct one.     

Radiochemical and biological characteristics of radioactive iodine labeled indomethacin for imaging of inflammation

Summary Indomethacin was successfully labeled with ¹²⁵I. This labeling reaction was carried out via electrophilic substitution of hydrogen atom with the iodonium atom I⁺. The reaction was found to be strongly dependent on pH of the reaction medium. At neutral pH value, 7 the labeling yield was maximum. This may be due to the good solubility of indomethacin, good protonation and good working of the oxidizing agent at this pH value. Towards the acidic pH value, the yield decreased and towards the alkaline pH value the yield decreased due to the decomposition of the indomethacin. The labeling reaction is very fast but needs five minutes for completion. The produced ¹²⁵I-indomethacin was found stable in-vivo as the thyroid gland uptake did not exceed 2%. Labeled indomethacin shows a good localization in inflamed muscle, either septic or sterile. It excretes mainly via liver and to some extent via kidney. The imaging must be carried out at 24-hour post injection, after that time, the background activity has cleared and the activity is concentrated in the target site.     

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.