Preparation of Radiolabeled Zolbetuximab Targeting CLDN18.2 and Its Preliminary Evaluation for Potential Clinical Applications.

Claudin18.2 (CLDN18.2), due to its high expression in various gastric cancer tissues, is considered an optimal target for antitumor drug molecules. In this study, we obtained the labeled compounds of [125I]I-zolbetuximab using the Iodogen method. Under the optimum labeling conditions, the molar activity of [125I]I-zolbetuximab was 1.75 × 102 GBq/µmol, and the labeling efficiency was more than 99%. The labeled compounds exhibited excellent in vitro stability in both phosphate buffer saline (PBS, pH = 7.4) and fetal bovine serum systems (FBS) (radiochemical purity >90% at 72 h). The uptake percentage of [125I]I-zolbetuximab in MKN45-CLDN18.2 cells is 24.69 ± 0.84% after 6 h. The saturation binding assay and specificity assay further demonstrated the high specificity of [125I]I-zolbetuximab for CLDN18.2. The long retention at the tumor site and rapid metabolic clearance at other organ sites of [125I]I-zolbetuximab were observed in small-animal SPECT-CT imaging. The same trend was also observed in the biodistribution study. Due to the excellent targeting ability of zolbetuximab for CLDN18.2, [125I]I-zolbetuximab exhibits strong specific binding and retention with cells and tumors highly expressing CLDN18.2. However, the balance between mAb's longer cycle time in vivo and targeting binding and retention ability should be intensively considered for using this kind of radiopharmaceutical in the diagnosis and treatment of CLDN18.2-positive gastric cancer.

Activity Measurement of Iodine Fission Products in 2LiF-BeF2 Salt and Its Application in Redox Potential Surveillance for a Thorium Molten Salt Reactor.

The activities of 131I, 132I, 133I, and 135I produced by neutron-induced fission of 235U in 2LiF-BeF2 (FLiBe) eutectic salt and their dependence on the redox potential were studied. The dependence observed experimentally suggested that the activity ratio for 131I to 132I could be used as an indicator of the redox potential for FLiBe salt. Relying on the selective adsorption of iodine ions on the activated silver probe by ion exchange, a novel method for activity distribution measurement of the iodine isotopes in FLiBe salt was founded. The method is simple, fast, and easy to operate and would be suitable particularly to in situ monitor the redox potential of a thorium molten salt reactor, where the redox potential should keep at a high level to avoid possible safety risk induced by 233Pa deposition in the reactor.

Reusable fibrous adsorbent prepared via Co-radiation induced graft polymerization for iodine adsorption.

Volatile iodine released from nuclear power plant reactors is radiological hazard to environment and human's health because of their high fission yield and environmental mobility. The complexity of nuclear waste management motivated the development of solid-phase adsorbents. Herein, co-radiation induced graft polymerization (CRIGP) was employed in the graft polymerization of N-vinyl-2-pyrrolidone (NVP) onto polyethylene-coated polypropylene skin-core (PE/PP) fibers using electron beam (EB) irradiation. This work provides a one-step green synthetic approach to prepare iodine fibrous adsorbents without any chemical initiators or large amount of organic solvent. The original and modified PE/PP fibers were characterized by fourier transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric (TG) and scanning electron microscopy (SEM) to demonstrate the grafting of NVP onto the PE/PP fibers. The capacity of iodine absorbed by the PE/PP-g-PNVP fibers was 1237.8 mg/g after 180 min. Meanwhile, absorbents can be regenerated efficiently by two different means of ethanol elution and heating at 120 °C, respectively. Within 10 min, 94.17% and 90.12% of the iodine can be released from the PE/PP-g-PNVP fibers with these two methods, respectively. The adsorbent exhibited a long service life of at least ten adsorption-desorption cycles, suggesting that PE/PP-g-PNVP fibers might be a promising adsorbent for volatile iodine adsorption from fission products in nuclear power plant reactors.

Coordination Structures of the Uranyl(VI)-Diamide Complexes: A Combined Mass Spectrometric, EXAFS Spectroscopic, and Theoretical Study.

The coordination structures of a series of uranyl-diamide complexes, namely UO2(TMGA)22+, UO2(TMTDA)22+, and UO2(TMPDA)22+ (TMGA: N, N, N', N'-tetramethylglutaramide; TMTDA: N, N, N', N'-tetramethyl-3-thiodiglycolamide; TMPDA: N, N, N', N'-tetramethylpyridine-2,6-dicarboxamide), in the gas phase and solution were studied by electrospray ionization (ESI) mass spectrometry, density functional theory (DFT) calculations, and extended X-ray absorption fine structure (EXAFS) spectroscopy. ESI of UO2Cl2-TMGA, UO2Cl2-TMTDA, and UO2Cl2-TMPDA solutions produced UO2(TMGA)22+, UO2(TMTDA)22+, and UO2(TMPDA)22+ as the major complexes in the gas phase. The gas-phase fragmentation patterns of these three complexes upon collision-induced dissociation (CID) are quite similar, and the products arising from (CH3)2N-COcarbonyl, CH2-COcarbonyl, Cpyridine-COcarbonyl, and CH2-CH2/S bond cleavages were identified, which agree with the degradation patterns of diamides upon γ irradiation in solution. DFT calculations revealed similar bidentate coordination modes of TMGA and TMTDA in the UO2(TMGA)22+ and UO2(TMTDA)22+ complexes in the gas phase. For UO2(TMPDA)22+, UO22+ is coordinated by two Ocarbonyl and one Npyridine from each TMPDA, which acts as a tridentate ligand. The results from EXAFS analysis indicate that the coordination structures of UO2(TMGA)22+, UO2(TMTDA)22+, and UO2(TMPDA)22+ in solution are similar to those in the gas phase.

Infrared Spectroscopic and Theoretical Studies of Group 3 Metal Isocyanide Molecules.

A series of group 3 metal isocyanide complexes were prepared via the reactions of laser ablated scandium, yttrium, and lanthanum atoms with (CN)2 in an argon matrix. The product structures were identified on the basis of their characteristic infrared absorptions from isotopically labeled (CN)2 samples as well as the calculated frequencies and isotopic frequency ratios. Group 3 metal atoms reacted with (CN)2 to form M(NC)2 (M = Sc, Y, La) when the samples were subjected to λ > 220 nm irradiation. Other products such as M(NC)3 and MNC were produced together with M(NC)2 through either the reactions of M(NC)2 and (CN)2 or the loss of one CN ligand from M(NC)2. CCSD(T)//B3LYP calculations reveal that ScNC possesses a 3Δ ground state, while 1Σ+ is most stable for YNC and LaNC. All of the M(NC)2 and M(NC)3 complexes were predicted to have doublet and singlet ground states, respectively. Group 3 metal cyanides are less stable than the isocyanides by at least 4 kcal/mol at the CCSD(T) level, and their C-N stretches are much weaker than the N-C stretches of the isocyanides. No absorption can be assigned to the M(CN) x complex, which would appear between 2100 and 2250 cm-1.

Formation and Characterization of Homoleptic Thorium Isocyanide Complexes.

Homoleptic thorium isocyanide complexes have been prepared via the reactions of laser-ablated thorium atoms and (CN)2 in a cryogenic matrix, and the structures of the products were characterized by infrared spectroscopy and theoretical calculations. Thorium atoms reacted with (CN)2 under UV irradiation to form the oxidative addition product Th(NC)2, which was calculated to have closed-shell singlet ground state with a bent geometry. Further reaction of Th(NC)2 and (CN)2 resulted in the formation of Th(NC)4, a molecule with a tetrahedral geometry. Minor products such as ThNC and Th(NC)3 were produced upon association reactions of CN with Th and Th(NC)2. Homoleptic thorium cyanide isomers Th(CN)x (x = 1-4) are predicted to be less stable than the corresponding isocyanides. The C-N stretches of thorium cyanides were calculated to be between 2170 and 2230 cm-1 at the B3LYP level, more than 120 cm-1 higher than the N-C stretches of isocyanides and with much weaker intensities. No experimental absorptions appeared where Th(CN)x should be observed.

Coordination Structure and Fragmentation Chemistry of the Tripositive Lanthanide-Thio-Diglycolamide Complexes.

Tripositive Ln(TMTDA)33+ complexes (Ln = La-Lu except Pm, TMTDA = tetramethyl 3-thio-diglycolamide) were observed in the gas phase by electrospray ionization of LnCl3 and TMTDA mixtures. Collision-induced dissociation (CID) was employed to investigate their fragmentation chemistry, which revealed the influence of metal center as well as ligand on the ligated complexes. Ln(TMTDA)2(TMTDA-45)3+ resulting from Ccarbonyl-N bond cleavage of TMTDA and hydrogen transfer was the major CID product for all Ln(TMTDA)33+ except Eu(TMTDA)33+, which predominantly formed charge-reducing product EuII(TMTDA)22+ via electron transfer from TMTDA to Eu3+. Density functional theory calculations on the structure of La(TMTDA)33+ and Lu(TMTDA)33+ revealed that Ln3+ was coordinated by six Ocarbonyl atoms from three neutral TMTDA ligands, and both complexes possessed C3h symmetry. The Sether atom deviating from the ligand plane was not coordinated to the metal center. On the basis of the CID results of Ln(TMTDA)33+, Ln(TMGA)33+, and Ln(TMOGA)33+, the fragmentation chemistry associated with the ligand depends on the coordination mode, while the redox chemistry of these tripositive ions is related to the nature of both metal centers and diamide ligands.

Matrix Infrared Spectra of Manganese and Iron Isocyanide Complexes.

Mono and diisocyanide complexes of manganese and iron were prepared via the reactions of laser-ablated manganese and iron atoms with (CN)2 in an argon matrix. Product identifications were performed based on the characteristic infrared absorptions from isotopically labeled (CN)2 experiments as compared with computed values for both cyanides and isocyanides. Manganese atoms reacted with (CN)2 to produce Mn(NC)2 upon λ > 220 nm irradiation, during which MnNC was formed mainly as a result of the photoinduced decomposition of Mn(NC)2. Similar reaction products FeNC and Fe(NC)2 were formed during the reactions of Fe and (CN)2. All the product molecules together with the unobserved cyanide isomers were predicted to have linear geometries at the B3LYP level of theory. The cyanide complexes of manganese and iron were computed to be more stable than the isocyanide isomers with energy differences between 0.4 and 4 kcal/mol at the CCSD(T) level. Although manganese and iron cyanide molecules are slightly more stable according to the theory, no absorption can be assigned to these isomers in the region above the isocyanides possibly due to their low infrared intensities.

Infrared Spectroscopic and Theoretical Studies on the OMF2 and OMF (M = Cr, Mo, W) Molecules in Solid Argon.

Group 6 metal oxide fluoride molecules in the form of OMF2 and OMF (M = Cr, Mo, W) were prepared via the reactions of laser-ablated metal atoms and OF2 in excess argon. Product identifications were performed by using infrared spectroscopy, 18OF2 samples, and electronic structure calculations. Reactions of group 6 metal atoms and OF2 resulted in the formation of ternary OCrF2, OMoF2, and OWF2 molecules with C2v symmetry in which the tetravalent metal center is coordinated by one oxygen and two fluorine atoms. Both OCrF2 and OMoF2 are computed to possess triplet ground states, and a closed shell singlet is the ground state for OWF2. Triatomic OCrF, OMoF, and OWF molecules were also observed during sample deposition. All three molecules were computed to have a bent geometry and quartet ground state. A bonding analysis showed that the OMF2 molecules have highly ionic M-F bonds. 3OCrF2 and 3OMoF2 have an M-O double bond composed of a σ bond and a π bond. 1OWF2 has an M-O triple bond consisting of a σ bond, a π bond, and a highly delocalized O lone pair forming the other π bond. The M-O bonds in the OMF compounds have triple-bond character for all three metals.

Effect of oxide impurities on the dissolution behavior of Th4+, Be2+ and U4+ in fluoride salts.

Oxides are one of the most important impurities in the fuel salt of molten salt reactors (MSRs), and excessive oxide impurities pose a risk to the safe operation of MSRs. This study focused on investigating the precipitation behavior between Th4+, U4+, and Be2+ with O2- in the 2LiF-BeF2 (FLiBe) eutectic salt system. The results showed that the solubility of UO2 was 5.52 × 10-3 mol kg-1, and the solubility product (Ksp) of UO2 was 6.14 × 10-7 mol3 kg-3 in FLiBe salt at 650 °C. It was also found that the O2- ion would firstly react with U4+ to form UO2, and then the excessive O2- would react with Be2+ to generate BeO in the FLiBe system. Despite conducting the solubility experiment of ThO2 and titration experiment of FLiBe-ThF4, the system failed to achieve the solubility and the Ksp of ThO2. The main reason for this was that O2- preferentially reacted with Be2+ over Th4+ to form precipitates, in other words, Be2+ exerted a protective effect against Th4+. Above all, this work experimentally demonstrated that in the FLiBe system, O2- preferentially combines with U4+ to form a precipitate, followed by Be2+, while Th4+ is relatively inert.

Control and surveillance of redox potential for 233Pa dissolution in 2LiF-BeF2 molten salt.

233Pa, the precursor nuclide of 233U in the thorium-uranium conversion is prone to reductive deposition in 2LiF-BeF2 (66 : 34 mol%, FLiBe) molten salt. We explored the adjustment and control of the redox potential of the FLiBe melt to avoid the 233Pa reduction deposition. The experimental data indicated that the deposited 233Pa can be completely dissolved and reentered into the molten salt with the addition of oxidant NiF2, and the distribution and behaviour of uranium, thorium, neptunium, and most fission products did not have any significant change in the NiF2-oxidised FLiBe molten salt, showing the feasibility of this manner to make 233Pa exist stably in the melt. The effects of NiF2-addition on the behaviour of the fission products 95Nb and 131I in the FLiBe molten salt were also investigated. It was found that 131I could be used as a redox indicator to monitor the redox potential of the oxidation-enhanced FLiBe molten salt. All the information drawn from this study could provide significant support for the control and surveillance of the redox potential of the FLiBe molten salt in the upcoming thorium molten salt reactor (TMSR).

Recovery of FLiBe from ThF4-FLiBe salt using precipitation-distillation coupled method.

The low-pressure distillation of FLiBe salt containing ThF4 was carried out at 1223 K and <10 Pa using thermogravimetric equipment. The weight loss curve indicated a rapid distillation stage at the beginning of distillation, followed by a slow stage. The composition and structure analyses showed that the rapid distillation process originated from the evaporation of LiF and BeF2, while the slow distillation process was mainly attributed to the evaporation of ThF4 and LiF complexes. Precipitation-distillation coupled method was employed for the recovery of FLiBe carrier salt. XRD analysis indicated that ThO2 was formed and remained in the residue with the addition of BeO. Our results showed that the combination of precipitation and distillation treatment was an effective way to recover carrier salt.

Distribution and behaviour of 233Pa in 2LiF-BeF2 molten salt.

Distribution and behavior of 233Pa, essential in the thorium-uranium nuclear fuel cycle, were studied in 2LiF-BeF2 (66 : 34 mole%, FLiBe) molten salt by γ-ray spectrometry. The experiments showed that 233Pa deposited slightly on the surface of graphite crucible. The addition of Hastelloy and metallic lithium decreased the 233Pa specific activity in the salt by 1 to 2 orders of magnitude rapidly. Analysis indicated that reductive deposition of 233Pa was responsible for the rapid decrease of 233Pa specific activity in the salt. Additional experiments strongly supported the mechanism of reductive deposition of 233Pa induced by Hastelloy and metallic lithium. In view of the large deposition of 233Pa on Hastelloy, the possible influence of fissile nuclide 233U produced from 233Pa decay on the operation of thorium-based molten salt reactor was discussed.

Evaporation behavior of 2LiF-BeF2-ZrF4 molten salt with irradiated nuclear fuel.

The evaporation behaviours of various components were investigated by using a low pressure distillation method in a 2LiF-BeF2-ZrF4 mixture containing irradiated ThF4 and UF4. The experiment showed that BeF2 and ZrF4 were found to mainly condensate at the outer cover, the coolest zone, and their relative volatilities vs. LiF were 9.8 and 32.2, respectively, while for ThF4 and UF4, at four different temperature zones the values were almost constant, at 0.1 and 0.3. The radioactivity of various nuclides was further detected using gamma spectrometer analysis. 137Cs was hardly observed due to long half-time decay. 233Pa was found to co-evaporate with the carrier salt, while 239Np mainly remained in the residual salt as 237U. In different temperature zones, the decontamination factors of rare earth in receiver salts ranged from 10 to 103. On the basis of the investigation, it was proposed that the distribution of various nuclides after distillation, may be helpful to design the feasible condensate system to recover the carried salt in a molten salt reactor.

Transient release of radioactive iodine from the fission of UF4 in 2LiF-BeF2 salt.

In this study, the behavior of fission product iodine released from the melting process of a mixture consisting of UF4 irradiated with neutrons and 2LiF-BeF2 (FLiBe) salt was studied. The experiment showed that a large amount of iodine was released immediately during melting and captured by Ni metal foils. The transient release of iodine observed in this experiment is attributed to the redox reaction between the hot atoms of the fission product iodine that cumulated due to long-time irradiation. The effect of the redox status of the molten salt on the transient release of iodine was also investigated. Based on this investigation, it was proposed that the activity ratios of 131I to salt-seeking fission products in the fuel salt, as an effective diagnostic criterion, may be used for the surveillance of the redox potential of fuel salts in a molten salt reactor.

UiO-66-NH-(AO) MOFs with a New Ligand BDC-NH-(CN) for Efficient Extraction of Uranium from Seawater.

Metal-organic frameworks (MOFs) with a high surface area and excellent stability are potential candidates for uranium (U) adsorption. Amidoxime (AO) is the most widely used functional group to extract U, which is usually introduced into MOFs by two-step post-synthetic methods (PSMs). Herein, MOF UiO-66-NH-(AO) was obtained by a one-step PSM with amidoximation from UiO-66-NH-(CN), which was synthesized by a new organic ligand of 2-cyano-terephthalic acid and whose morphology was octahedron and could be well controlled with the new ligand. The one-step PSM can greatly maintain the octahedron of the MOFs. What is more, UiO-66-NH-(AO) showed good adsorption performance for U, the adsorption equilibrium was obtained within 1500 min, and the adsorption capacity of U was calculated to be 134.1 mg/g according to the Langmuir model. It also had excellent selectivity for U in the presence of high concentrations of vanadium (V), ferrum (Fe), magnesium (Mg), calcium (Ca), and zirconium (Zr). The adsorption capacity of U in natural seawater was determined to be 5.2 mg/g within 8 days. The recyclability of UiO-66-NH-(AO) in simulated seawater was demonstrated for at least four adsorption/desorption cycles. The binding mechanism was investigated by the extended X-ray absorption fine structure spectroscopy, revealing that U binding occurs in a fashion η2 motif. This study provides a reliable idea for the modification of MOFs and the potential for MOF-based materials to extract U from seawater.

The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction.

Although the protective effect of the polyhydroxylated fullerene derivative C(60)(OH)(n) against ionizing radiation is an area of much interest, the mechanisms relating to how polyhydroxylated fullerene derivatives improve mitochondrial dysfunction remain unknown. In order to find new and effective radioprotective agents, we synthesized a new polyhydroxylated fullerene molecule with 24 hydroxyl groups of known positions on C(60) and studied its protective effects in mice subjected to irradiation. Mice were pretreated with C(60)(OH)(24) for 2 weeks (daily, 40 mg/kg i. p.), then subjected to a lethal dose of whole body gamma-irradiation (from a (60)Co source). Survival was observed for 30 days after irradiation. Immune and mitochondrial dysfunction and oxidative damage were analyzed in mice with the same C(60)(OH)(24) pretreatment and irradiation except that the animals were euthanized at day 5 after the irradiation. It was found that 2-week C(60)(OH)(24) pretreatment effectively reduced whole body irradiation-induced mortality without apparent toxicity. C(60)(OH)(24) pretreatment also showed significant protective effects against ionizing-radiation-induced decreases in immune and mitochondrial function and antioxidant defense in the liver and spleen. These results suggest that the polyhydroxylated fullerene derivative C(60)(OH)(24) protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.

Systematic influence induced by 3 nm titanium dioxide following intratracheal instillation of mice.

This work reported the systematic influence of titanium dioxide nanoparticles (TiO2 NPs) with a diameter of 3 nm on mice. Mice were repeated intratracheally instilled with TiO2 NPs, once per-week for 4 consecutive weeks, at total dose of 13.2 mg/kg. At 28 days post-instillation, the biochemical parameters in broncboalveolar lavage fluid (BALF) and brain homogenate as well as histopathologic changes of tissues were examined to describe the subacute toxicity of instilled TiO2 NPs. The results showed that instilled TiO2 NPs could induce lung damage, and change the permeability of alveolar-capillary barrier. The TiO2 NPs were able to get access to blood circulation and reach extrapulmonary tissues, then lead to injury at the different level, such as liver and kidney. Our results also indicated that TiO2 NPs might pass through the blood-brain barrier (BBB), and induce the brain injury through oxidative stress response.

Preparation and characterization of a new hydrophilic C60 derivative (OH)16C60CHCOOH.

C60 and its derivatives are very important nanomaterials in biological and materials science. Unfortunately, due to the high hydrophobicity of the C60 cage, most of these materials are insoluble in water and their usages are quitely restricted. Here we reported the preparation and characterization of (OH)16C60CHCOOH, a new multihydroxylated methanofullerene carboxylic acid (MMFCA) derivative with high aqueous solubility. The elementary analysis, FT-IR and 1HNMR confirmed the structure of this material. Like other C60 and its derivatives, this new derivative also contains the free radical scavenging ability, measured by electron spin resonance (ESR) test. On the other hand, the MTT assay showed it had low cytotoxicity. Therefore, this new MMFCA derivative might be a potential vehicle for the introduction of hydrophobic C60 derivatives into water or a hydrophilic environment.

The acute pulmonary toxicity in mice induced by multiwall carbon nanotubes, benzene, and their combination.

Carbon nanotubes (CNTs) have been synthesized and produced on large scale for their wide application. They have high absorption ability to organic contaminants (such as benzene) and can form CNTs-benzene combination with benzene. In this article, the acute pulmonary toxicity, induced by multiwall carbon nanotubes (MWCNTs), benzene, and their combination, was studied by administrating the three test materials into mice lungs via intratracheal instillation. The biochemical parameters in bronchoalveolar lavage fluid (BALF) and pathological lesions in lungs were used as endpoints to evaluate the pulmonary toxicity of the three test materials at 3-day and 7-day postexposure, respectively. After the mice were intratracheally instilled with MWCNTs, benzene and MWCNTs-benzene combination at doses of 6.67 mg/kg, 2.67 mg/kg, and 9.34 mg/kg (containing 6.67 mg/kg MWCNTs and 2.67 mg/kg benzene), the total protein, alkaline phosphatase (ALP), acid phosphatase (ACP), and lactate dehydrogenase (LDH) in BALF and pathological lesions in lungs were examined. At 3-day postexposure, MWCNTs induced obvious pulmonary toxicity and benzene only induced slight pulmonary toxicity, whereas their combination induced very severe pulmonary toxicity. At 7-day postexposure, MWCNTs and benzene did not induce pulmonary toxicity individually, whereas their combination still induced severe pulmonary toxicity. These data indicated that, at the instilled doses in this experiment, the MWCNTs can alone induce acute pulmonary toxicity in mice and the benzene does not induce pulmonary toxicity, but the pulmonary toxicity of MWCNTs is enhanced after they form MWCNTs-benzene combination with low dose of benzene. The enhanced pulmonary toxicity may be due to the change of MWCNTs aggregation ability after benzene is adsorbed on them.