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.     

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 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.     

Radioiodination of insulin using N-succinimidyl 5-(tributylstannyl)-3-pyridine-carboxylate (SPC) as a bi-functional linker: Synthesis and biodistribution in mice</p> </p>

Summary Insulin receptors are overexpressed on a number of human tumors, leading to significant affinity of insulin to these tumors. It is appealing to receptor-targeted radiotherapy for malignant tumors if insulin is labeled with suitable radionuclide. In this paper, N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate (SPC), a potential bi-functional linker for radioiodination of proteins or peptides, was synthesizedby using 5-bromonicotinic acid as the starting material. Then, with this bi-functional linker, insulin was conjugated with ¹³¹I, and the tissue distribution of the labeled insulin (¹³¹I-SIPC-insulin) in normal mice was investigated. The results showed that insulin ^</span> could be conjugated with¹³¹I using SPC as the linker ^</span> in a labeling yield of40-58%, and with radiochemical purity of more than 98% after purification bySephadex?G-10. Even kept at room temperature for 72 hours, the radiochemical purity of ¹³¹I-SIPC-insulin was still more than 97%, implying that the conjugated insulin was constantly stable in vitro.Meanwhile, in order to evaluate the in vivo stability of the conjugated compounds, insulin was also labeled with ¹³¹I by a direct method using chloramine-T (Ch-T) as the electrophilic agents.Biodistribution of¹³¹I-SIPC-insulinin micesuggested that ¹³¹I could clear rapidly from the blood,mainly excreted by kidney. However, ¹³¹I uptake of mice with¹³¹I-SIPC-insulin in some key organs, especially in thyroid and stomach, were much less (150 or 30 times) than that with the direct labeled insulin (¹³¹I-insulin). Additionally, it was noted that ¹³¹I-SIPC-insulin hasmuch betterinvivo stability than¹³¹I-insulin.</p> </p>     

Labeling of Sertraline with 131I and investigation of its radiopharmaceutical potential

Sertraline is an antidepressant drug. Sertraline was labeled with ¹³¹I by using iodogen method. Labeling yield was 85–90% and specific activity was approximately 64.75 GBq/mmol. The purification of radioiodinated Sertraline was performed by Sep Pak C-18 plus and the radiochemical purity was determined to be over 99%. Biodistribution studies were carried out by male Albino Wistar rats. The percentage of injected radioactivity per gram of tissue was calculated, and these data versus time curves were generated for organs and brain regions. The results showed that ¹³¹I labeled Sertraline may be a promising radiopharmaceutical for the investigation of serotonin 5-HT receptor functions of brain.     

Biological distribution of iodo-allyl gabapentin and iodo-gabapentin

Gabapentin (GBP) is an anticonvulsant and is widely used in the treatment of epilepsy. In this study, GBP and an allyl derivative of GBP were radioiodinated with ¹³¹I using the iodogen method; then their radiopharmaceutical potential in rats and rabbits was investigated. The radiochemical purity of ¹³¹I-GBP and its derivatives was determined by RTLC. The labeling yield was 95±2%. Biological evaluation was performed in normal rats and rabbits. Labeled compounds were intravenously injected into two rabbits via the ear vein after anesthetizing. The dynamic and static scintigrams were obtained using a gamma camera at different time. Then the labeled compounds were administered intravenously into the rats. The distribution was studied by counting the radioactivity in the removed organs. The results of biodistribution in the rats showed the clearance of ¹³¹I-ALGBP was faster than ¹³¹I-GBP. On the other hand, the uptake of ¹³¹I-ALGBP in the brain was higher than ¹³¹I-GBP at 60 minutes.     

Preparation of <Superscript>131</Superscript>I–betulinic acid and its biodistribution in murine model of hepatocellular tumor

The aim of this study was to examine the radioiodinating condition of betulinic acid and understand the possibility of ¹³¹I–betulinic acid (¹³¹I–BA) as a potential tumor radiotherapy agent through in vitro uptake and in vivo biodistribution studies ¹³¹I–BA was prepared by the reaction of betulinic acid with Na¹³¹I in the presence of hydrogen peroxide, and then purified by HPLC. The labeling yield was about 80%, and the radiochemical purity was greater than 95%. ¹³¹I–BA was found to be stable at 4 °C in saline containing 1% ethanol. In vitro studies showed that ¹³¹I–betulinic acid accumulated in the cancer cell lines (BEL-7402 and NCI-H446) in comparison with free ¹³¹I⁻. In vivo biodistribution study in KM mice bearing HepA tumor showed that ¹³¹I–BA stayed longer time in tumors than free ¹³¹I⁻. A significant differences were seen in tumor/muscle ratio at 4 h postinjection between ¹³¹I–BA and free ¹³¹I⁻. In vivo and in vitro studies showed the higher fraction of ¹³¹I–BA can be utilized for therapy and a higher dose will be delivered per targeting event. ¹³¹I–BA is a promising radiopharmaceutical in nuclear medicine, especially for hepatocellular tumor targeted radionuclide brachytherapy.     

Synthesis of radioiodinated 4-[*I]iodoantipyrine via isotopic exchange

Radioiodinated 4-[*I]iodoantipyrine labeled with radioiodine (i.e., ¹²³I or ¹²⁵I or ¹³¹I) has been used for modeling radiation damage on cell nuclei of tumor cells where the characteristic high linear energy transfer (high-LET) of the Auger electron could be demonstrated. Also, the compound is currently used for the measurement of regional cerebral blood flow (rCBF) in autoradiography. 4-[¹³¹I]iodoantipyrine was synthesized by two methods via a nucleophilic isotopic exchange reaction between ¹³¹I as iodide ion [¹³¹I^–] and inactive 4-[¹²⁷I]iodoantipyrine: either in absolute ethyl alcohol catalyzed by ammonium acetate or in dry state molten ammonium acetate (m.p. 114 °C) as an isotopic exchange medium without carrier addition. The first one is called wet method: where a solution of 4-iodoantipyrine and ammonium acetate in absolute ethyl alcohol and lyophilized Na¹³¹I was heated briefly up to boiling (80 to 90 °C) for 30 minutes under reflux. The second one is called dry state-molten method: where the alcoholic solution containing 4-iodoantipyrine and ammonium acetate and the lyophilized Na¹³¹I were heated briefly in a nitrogen stream to dryness at 120 to 125 °C for 5 minutes or melted by gradual heating at 150 to 160 °C for 5 minutes. A radiochemical yield ranged between 90%–95% in each method has been obtained for 4-[¹³¹I]iodoantipyrine. In both methods, the reaction proceeds properly without carrier addition by an addition – elimination mechanism. The physico-chemical parameters affecting the radiochemical yield of the isotopic exchange reaction [i.e., reaction time, temperature, exchange medium, concentration of the reactants, carrier (KI) addition and pH] were investigated. Chromatographic analysis i.e., TLC and HPLC were used to determine the radiochemical yield as well as the purity of the final product, which was as pure as 99.9%.     

Radio TLC in quality control and development of radiopharmaceuticals

Radio TLC has been used for determining the radiochemical purity and composition of two^99mTc-radiopharmaceuticals, available as kits and commonly used for diagnostic imaging. Moreover, the same technique has been applied to detect impurities which decrease the specific activity of¹³¹I-derivatized dermatan sulfate, a new potential radiopharmaceutical, and for establishing the best labeling conditions.     

新型除草剂丙酯草醚A环14C均标记合成和鉴定

以U-¹⁴C-对氨基苯甲酸为前体, 通过酯化、缩合、还原和取代四步反应获得了A环¹⁴C均标记的丙酯草醚, 用PHPLC对其进行纯化. 采用HPLC-MS(ESI), MS(EI)和¹H NMR验证了其结构, 通过HPLC(外标法)确定其化学纯度大于98%; HPLC-LSC和TLC-IIA两种方法分析表明, 其放射化学纯度大于98%, 其比活度为1.089±0.011 mCi/mmol. 合成的化学收率和放化收率均为53%.     

An improved method for the preparation of [<Superscript>14</Superscript>C]thiourea of high radiochemical purity

Summary An improved method for the preparation of [¹⁴C]thiourea of high radiochemical purity is described. [¹⁴C]thiourea is prepared by the barium cyanamide route and is purified by vacuum-sublimation. The labeled product showed ammonium [¹⁴C]thiocyanate as a radiochemical impurity in the range of 2-4%. This was further purified by silica-gel column chromatography to get the product having more than 99% radiochemical purity.     

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 rapid and high-yield aqueous phase preparation procedure for123I-labelled meta-iodobenzylguanidine

A new, aqueous phase preparation procedure for¹²³I-mIBG /meta-iodobenzylguanidine/ is described. It comprises a copper-catalyzed exchange reaction between aqueous¹²³I-iodide and mIBG at 150 °C for 45 min, a purification via anion-exchange chromatography, and a sterilization via micropore filtration. Overall preparative yield, radiochemical purity and specific activity amount to >90%, >99.7% and >10¹⁵ Bq.mol^–1 mIBG, respectively. Other features are simplicity /no evaporation of water or other solvents/, reproducibility of labelling yield and radiochemical purity, and speed /total time required 1.5 h/.     

Partition coefficient of [3H] stobadin: Its application as an indicator of radiochemical purity

A simple and rapid method is described for the estimation of the radiochemical purity of [³H] stobadin. The proposed method uses the value of the partition coefficient /P/ as an indicator of radiochemical purity.     

Optimization of the production of [61Cu]Diacetyl-bis(N 4-methylthiosemicarbazone) for PET studies

Summary Copper-61 produced via the ^natZn(p,x)⁶¹Cu nuclear reaction was used for the preparation of [⁶¹Cu]diacetyl-bis(N⁴-methylthiosemicarbazone) ([⁶¹Cu]ATSM) (4) using a house-made ATSM ligand. After a proton irradiation of an electroplated zinc layer by 22 MeV protons at 180 mA for 3.2 hours, ⁶¹Cu was recovered by two-step chromatography using a cation and an anion exchange column. About 222 GBq (6.00 Ci) of ⁶¹Cu²⁺ was obtained with a radiochemical separation yield of more than 95% and a radionuclidic purity of better than 99%. Colorimetric methods showed that traces of chemical impurities in the product were below the accepted limits. The [⁶¹Cu]ATSM production was optimized for reaction conditions (buffer concentration and temperature) with a radiochemical yield of higher than 80%, radiochemical purity of better than 98% and a specific activity of about 246 Ci/mmol. The produced [⁶¹Cu]ATSM is a PET radiotracer for hypoxia imaging with an intermediate half life and a satisfactory quality, suitable for future PET studies.     

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.     

Stability of L-[S-methyl-11C]methionine solutions

For clinical PET studies L-[S-methyl-¹¹C]methionine ([¹¹C]MET) solutions have been prepared in both high doses and specific activities (up to 48.1 GBq and 370 GBq/mmol, respectively) with high radiochemical purity (>99%). The stability of these preparations was investigated by HPLC to ensure the radiopharmaceutical efficacy during the usable shelf life. Under our routine conditions the observed radiochemical purity loss never exceeded 3.5% one hour after EOS. The decomposition rate was affected by total activity and chemical composition of the solutions.     

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.     

双功能偶联剂SPC的一种新合成方法及其碘标记

放射性碘标记药物广泛用于医学检验及临床诊断和治疗中。放射性碘标记蛋白质不管是采用Ch-T、Iodogen直接标记方法还是采用Bolton-Hunter试剂间接标记方法,其存在的主要问题是标记物可能在体内严重脱碘[1,2]。为了克服这一问题,人们不断改进碘标记方法。其中,Zalutsky、W ilbur     

Labeling of ursodeoxycholic acid with technetium-99m for hepatobiliary imaging

An adopted method for the preparation of high radiochemical purity ^99mTc-ursodeoxycholic acid (UDCA) was conducted with a high radiochemical yield up to 97.5 %. The reaction proceeds well using 2 mg UDCA, 50 μg tin chloride in solution of pH 8 at room temperature for 30 min. The radiochemical yield was up to 97.5 % as pure as ^99mTc-UDCA. Different chromatographic techniques (paper chromatography and electrophoresis) were used to evaluate the radiochemical yield and purity of the labeled product. Biodistribution studies were carried out in Albino Swiss mice at different time intervals after administration of ^99mTc-UDCA. The uptake of ^99mTc-UDCA in the liver gave the chance to diagnose it. The results indicate that the labeled compound cleared from the systematic circulation within 2 h after administration and majority of organs showed significant decrease in uptake of ^99mTc-UDCA. Finally, the liver uptake was high and the results indicate the possibility of using ^99mTc-UDCA for hepatobiliary imaging.