Ha Eun Shim

Efficient method for iodine radioisotope labeling of cyclooctyne-containing molecules using strain-promoted copper-free click reaction

Herein we report an efficient method for iodine radioisotope labeling of cyclooctyne-containing molecules using copper-free click reaction. For this study, radioiodination using the tin precursor 2 was carried out at room temperature to give (125)I-labeled azide ([(125)I]1) with high radiochemical yield (85%) and excellent radiochemical purity. Dibenzocyclooctyne (DBCO) containing cRGD peptide and gold nanoparticle were labeled with [(125)I]1 at 37°C for 30min to give triazoles with good radiochemical yields (67-95%). We next carried out tissue biodistribution study of [(125)I]1 in normal ICR mice to investigate the level of organ accumulation which needs to be considered for pre-targeted in vivo imaging. Large amount of [(125)I]1 distributed rapidly in liver and kidney from bloodstream and underwent rapid renal and hepatobiliary clearance. Moreover [(125)I]1 was found to be highly stable (>92%) in mouse serum for 24h. Therefore [(125)I]1 could be used as a potentially useful radiotracer for pre-targeted imaging. Those results clearly indicated that the present radiolabeling method using copper free click reaction would be quite useful for both in vitro and in vivo labeling of DBCO group containing molecules with iodine radioisotopes.

Highly efficient method for 125I-radiolabeling of biomolecules using inverse-electron-demand Diels–Alder reaction

In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans-cyclooctene group conjugated biomolecules using inverse-electron-demand Diels-Alder reaction. Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give 125I-labeled azide ([125I]1) with high radiochemical yield (65±8%) and radiochemical purity (>99%). For radiolabeling application of [125I]1, trans-cyclooctene derived cRGD peptide and human serum albumin were prepared. These substrated were reacted with [125I]1 under mild condition to provide the radiolabeled products [125I]6 and [125I]8, respectively, with excellent radiochemical yields. The biodistribution study of [125I]8 in normal ICR mice showed significantly lower thyroid uptake values than that of 125I-labeled human serum albumin prepared by a traditional radiolabeling method. Therefore [125I]8 will be a useful radiolabeled tracer in various molecular imaging and biological studies. Those results clearly demonstrate that [125I]1 will be used as a valuable prosthetic group for radiolabeling of biomolecules.

Efficient and selective removal of radioactive iodine anions using engineered nanocomposite membranes

The efficient treatment of radioactive waste arising from nuclear accidents and overuse of radioisotopes has become an important issue, and much effort has been devoted to protecting the environment from such toxic radioactive materials. Among them, radioactive iodine in water is regarded as one of the most palpable threats to humans, as it is generated by post-use in medical and industrial applications. Although a few adsorbents and purification processes have been reported, the development of a better desalination method that is able to provide high removal efficiency, ion-selectivity, and reusability is still in demand. Herein, we report a hybrid composite membrane, composed of gold nanoparticles and cellulose acetate membranes, which has the potential to be used for efficient desalination of radioactive iodine. A single filtration process using this membrane provided high removal efficiency with more than two orders of magnitude iodide anion removal within a minute and excellent ion-selectivity. Moreover, the same operation can be applied several times without significant decrease of its performance. Therefore, it is anticipated that our work will be a new avenue for desalination of radioactive iodine in various aqueous media.

Synthesis and evaluation of an (125)I-labeled azide prosthetic group for efficient and bioorthogonal radiolabeling of cyclooctyne-group containing molecules using copper-free click reaction.

Herein we report the radiosynthesis of a pyridine derived azide prosthetic group for iodine radioisotope labeling of dibenzocyclooctyne (DBCO) conjugated molecules. The radiolabeling of the stannylated precursor 2 was conducted using [(125)I]NaI and chloramine-T to give (125)I-labeled azide ([(125)I]1) with high radiochemical yield (72±8%, n=4) and radiochemical purity (>99%). Using (125)I-labeled azide ([(125)I]1), cyclic RGD peptide and near infrared fluorescent molecule were efficiently labeled with modest to good radiochemical yields. The biodistribution study and SPECT/CT images showed that [(125)I]1 underwent rapid renal clearance. These results clearly demonstrated that [(125)I]1 could be used as an useful radiotracer for in vivo pre-targeted imaging as well as efficient in vitro radiolabeling of DBCO containing molecules.

An Efficient Method for Selective Desalination of Radioactive Iodine Anions by Using Gold Nanoparticles-Embedded Membrane Filter

Here, we demonstrate a detail protocol for the preparation of nanomaterials-embedded composite membranes and its application to the efficient and ion-selective removal of radioactive iodines. By using citrate-stabilized gold nanoparticles (mean diameter: 13 nm) and cellulose acetate membranes, gold nanoparticle-embedded cellulose acetate membranes (Au-CAM) have easily been fabricated. The nano-adsorbents on Au-CAM were highly stable in the presence of high concentration of inorganic salts and organic molecules. The iodide ions in aqueous solutions could rapidly be captured by this engineered membrane. Through a filtration process using an Au-CAM containing filter unit, excellent removal efficiency (>99%) as well as ion-selective desalination result was achieved in a short time. Moreover, Au-CAM provided good reusability without significant decrease of its performances. These results suggested that the present technology using the engineered hybrid membrane will be a promising process for the large-scale decontamination of radioactive iodine from liquid wastes.

Quantification of inhaled aerosol particles composed of toxic household disinfectant using radioanalytical method

To assess the risk posed by a toxic chemical to human health, it is essential to quantify its uptake in a living subject. This study aims to investigate the biological distribution of inhaled polyhexamethylene guanidine (PHMG) aerosol particle, which is known to cause severe pulmonary damage. By labeling with indium-111 (111In), we quantified the uptake of PHMG for up to 7 days after inhalation exposure in rats. The data demonstrate that PHMG is only slowly cleared, with approximately 74% of inhaled particles persisting in the lungs after 168 h. Approximately 5.3% of inhaled particles were also translocated to the liver after 168 h, although the level of redistribution to other tissues, including the kidneys and spleen, was minimal. These observations suggest that large uptake and slow clearance may underlie the fatal inhalation toxicity of PHMG in humans.

Development of a new thiol-reactive prosthetic group for site-specific labeling of biomolecules with radioactive iodine

In this report, we describe the radiosynthesis of a new thiol-targeting prosthetic group for efficient radioactive iodine labeling of biomolecules. Radioiodination using the precursor 3 was performed to obtain 125I-labeled tetrazole 4b with high radiochemical yield (73%) and radiochemical purity. Using the radiolabeled 4b, a single free cysteine containing peptide and human serum albumin were labeled with 125I in modest-to-good radiochemical yields (65-99%) under mildly reactive conditions. A biodistribution study of [125I]7 in normal ICR mice exhibited lower thyroid uptake values than those of 125I-labeled human serum albumin prepared via a traditional radiolabeling method. Thus, [125I]7 could be employed as an effective radiotracer for molecular imaging and biodistribution studies. The results clearly demonstrate that 4b has the potential to be effectively implemented as a prosthetic group in the preparation of radiolabeled biomolecules.

An Optimized Protocol for the Efficient Radiolabeling of Gold Nanoparticles by Using a 125I-labeled Azide Prosthetic Group.

Here, we demonstrate a detailed protocol for the radiosynthesis of a 125I-labeled azide prosthetic group and its application to the efficient radiolabeling of DBCO-group-functionalized gold nanoparticles using a copper-free click reaction. Radioiodination of the stannylated precursor (2) was carried out by using [125I]NaI and chloramine T as an oxidant at room temperature for 15 min. After HPLC purification of the crude product, the purified 125I-labeled azide (1) was obtained with high radiochemical yield (75 ± 10%, n = 8) and excellent radiochemical purity (>99%). For the synthesis of radiolabeled 13-nm-sized gold nanoparticles, the DBCO-functionalized gold nanoparticles (3) were prepared by using a thiolated polyethylene glycol polymer. A copper-free click reaction between 1 and 3 gave the 125I-labeled gold nanoparticles (4) with more than 95% of radiochemical yield as determined by radio-thin-layer chromatography (radio-TLC). These results clearly indicate that the present radiolabeling method using a strain-promoted copper-free click reaction will be useful for the efficient and convenient radiolabeling of DBCO-group-containing nanomaterials.