Latest ArticlesTumor-related PD-L2 expression is associated with the clinical efficacy of PD-1/PD-L1 blockade therapy. PD-L2-specific imaging can help selecting patients for appropriate immunotherapy. In this study, a PD-L2-targeting peptide (PDP2) was screened by the one-bead one-compound combinatorial library approach. Using the retro-inverso D-peptide of PDP2 (RD-PDP2) and PEGylation strategies, we developed a novel Tc-99m-labeled PD-L2-targeting peptide as a SPECT tracer (99mTc-PEG6-RD-PDP2) for imaging of tumor PD-L2 expression. The radiolabeling yield of 99mTc-PEG6-RD-PDP2 was greater than 95% by the standard HYNIC/tricine/TPPTS labeling procedure. 99mTc-PEG6-RD-PDP2 displayed high PD-L2-binding specificity both in vitro and in vivo. SPECT/CT imaging with 99mTc-PEG6-RD-PDP2 showed that the A549-PD-L2 tumors were clearly visualized, whereas the signals in PD-L2-negative A549 tumors were much lower. In vivo blocking study suggested that the tumor uptake of 99mTc-PEG6-RD-PDP2 was PD-L2 specifically mediated. 99mTc-PEG6-RD-PDP2 is a promising SPECT probe for the non-invasive imaging of tumor PD-L2 expression and has a great potential in guiding the anti-PD-1 or anti-PD-L1 immunotherapy of cancer.
Carbohydrate antigen 19-9 (CA19-9) with multi epitopes relatively high expresses on colorectal cancer (CRC) cells, making it an attractive target for developing radioimmunotherapy (RIT) for CRC. The lutetium-177 (177Lu) labeled monoclonal antibodies (mAbs) can selectively bind the corresponding antigens and release targeted cytotoxic radiation, which could induce cell apoptosis and reduce the drug-induced resistance. Here, a series of CA19-9 mAbs were labeled with zirconium-89 (89Zr), and one with high tumor uptake was screened via PET imaging, which has potential application for the diagnosis of CRC. Then the screened mAb (C003) labeled with 177Lu was utilized for CA19-9 targeted RIT, which presents a significant suppression effect on the growth of colo205 xenografts than immunotherapy alone. Meanwhile, the side effects of 177Lu-DOTA-C003 are limited according to the results of in vivo study. Both 89Zr-DFO-C003 for CRC immune-PET imaging and 177Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications.
Heavy haze events have become a serious environment and health problem in China and many developing countries, especially in big cities, like Beijing. However, the factors and processes triggered the formation of secondary particles from the gaseous pollutants are still not clear, and the processes driving evolution and degradation of heavy haze events are not well understood. Iodine isotopes (127I and 129I) as tracers were analyzed in time series aerosol samples collected from Beijing. It was observed that the 127I concentrations in aerosols peaked during the heavy haze events. The conversion of gaseous iodine to particular iodine oxides through photochemical reactions provides primary nuclei in nucleation and formation of secondary air particles, which was strengthened as the external iodine input from the fossil fuel burning in the south/southeast industrial cities and consequentially induced heavy haze events. Anthropogenic 129I concentrations peaked during clean air conditions and showed high levels in spring and later autumn compared to that in summer. 129I originated from the direct air discharges and re-emissions from contaminated seawaters by the European nuclear fuel reprocessing plants was transported to Beijing by the interaction of Westerlies and East Asian winter monsoon. Three types of mechanisms were found in the formation and evolution of heavy haze events in Beijing by the variation of 127I and 129I, i.e., iodine oxides intermediated secondary air particles, dust storm and mixed mode by both secondary air particles and dust storm induced processes.
Plutonium (Pu) is an anthropogenic radionuclide which mainly derived from atmospheric nuclear tests in the environment. In this study, the Pu isotopes (239Pu and 240Pu) in aerosol samples collected during the sandstorm and non-sandstorm period were measured by accelerator mass spectrometry (AMS) and the behavior of Pu was studied. The activity concentrations of 239Pu and 240Pu in the aerosol samples of Beijing were ranged from 0.62 nBq/m3 to 99.6 nBq/m3 for 239Pu and 3.51 nBq/m3 to 60.23 nBq/m3 for 240Pu, respectively. 239Pu and 240Pu concentrations exhibited a remarkable seasonal variation trend, with the higher results showed in spring, and the relatively lower concentrations in winter. The observed higher concentration of 239Pu and 240Pu detected in sandstorm samples further indicated Pu was closely related to the occurrence of sandstorms. The global fallout characteristics of 240Pu/239Pu atom ratios (average 0.20, ranging from 0.16 to 0.27) in aerosol samples indicating that global fallout was the major source of Pu in the atmosphere. Using aluminum (Al) as an indicator of soil resuspension, significant positive correlation between 239Pu and Al (r2 = 0.934), 240Pu and Al (r2 = 0.525) revealed that soil resuspension was a primary source of atmospheric Pu in Beijing. These results implied that the combination of 239Pu, 240Pu and Al could be used as the potential tracer of sandstorm.
The abundances of heavy elements produced in r-process nucleosynthesis in the early solar system need experimental verification. 244Pu could be the heaviest primordial nuclide produced before the formation of the Earth still being detectable today. As recent attempts failed to confirm the discovery of 244Pu signals at a concentration of 1.0 × 10−18 g/g in bastnaesite reported by Hoffman et al. in this study, the total primordial 244Pu in 450 g bastnaesite sample from Bayan Obo ore (China) was measured using ultra-sensitive compact accelerator mass spectrometry (AMS). As no 244Pu signal was detected, an upper limit for the 244Pu in our bastnaesite sample was estimated to be 2.1 × 10−20 g/g at 99% confidence level.
Two tetravalent uranium silicate and germanate M2UIVT3O9 (M = K, Cs; T = Si, Ge) crystals were crystalized under inert gas by molten salt flux growth method. K2USi3O9 (1) crystallizes in the monoclinic space group P121/n1 with lattice parameters a = 7.1076 Å, b = 10.4776 Å, c = 12.2957 Å, γ = 120° and V = 915.67 Å3. Cs2UGe3O9 (2) crystallizes in a hexagonal space group P-6 with lattice constants of a = 7.5138 Å, b = 7.5138 Å, c = 11.0114 Å, γ = 120° and V = 538.38 Å3. Bond valence calculations indicate tetravalent uranium in both structures, which contain three-membered single-ring T3O96− trimers. K2USi3O9 is the first uranium silicate that contains the Si3O96− trimers.
The complexation of pentavalent neptunium, Np(V), with nitrate ion in an ionic liquid solution has been studied spectroscopically for the first time. The characteristic f-f transition absorption band of Np(V) in the NIR region changes significantly upon the titration of nitrate ion into the solution, revealing strong complexation of Np(V) with nitrate ion in the ionic liquid. Most notably, the absorption band of Np(V) almost disappears when a sufficiently high concentration of nitrate ion is present in the solution. Such a rare optically "silent" species can be assigned to the 1:2 Np(V)/nitrate complex with a centrosymmetric coordination environment where Np sits at the inversion center.
Due to the rigid Si-O-Si backbone, silicone rubber (SR) have a widespread application in extreme environment such as high temperature and high-level radiation. However, the radiation stability of SR still does not meet the practical needs in special radiation environments. Herein we prepared epoxy POSS(ePOSS)/SR nanocomposites with excellent thermal stability and radiation resistance. As a physical crosslinking point in the SR, addition of small amount of ePOSS not only enhanced the mechanical properties of the matrix, but also improved its thermal stability greatly due to their good compatibility. ePOSS/SR had higher radiation stability in air than SR owing to the inhibition of radiation oxidation by ePOSS, and the yield of main gaseous radiolysis products (CH4, H2, CO and CO2) of SR and ePOSS/SR nanocomposites was determined. By analyzing the changes of chemical structure, thermal properties and mechanical properties of the ePOSS/SR nanocomposite, combined with the characteristics of gas products after γ-irradiation, the radiation induced crosslinking and degradation mechanism of the nanocomposites was proposed comprehensively.
Actinide metallacycles are an emerging class of functional coordination assemblies, but multi-level assembly from metallacycle units toward hierarchical supramolecular structures are still rarely investigated. In this work, we put forward a novel supramolecular inclusion-based method through introducing two macrocyclic hosts, cucurbit[7]uril (CB[7]) and cucurbit[8]uril (CB[8]) to facilitate hierarchical assembly of uranyl metallacycles with higher complexity, and successfully prepare two different kinds of uranyl metallacycle-based complexes with intriguing hierarchical structures, a CB[7]-based four-member molecular necklace ([4]MN) and a CB[8]-involved ring-in-ring supramolecular polymer chain. The results obtained here prove the feasibility of supramolecular inclusion for regulating coordination assembly of uranyl metallacycles and related hierarchical structures. It is believed that this method can be used to achieve the construction of actinide coordination assemblies with higher structural complexity.
Racemic [18F]FBFP ([18F]1) proved to be a potent σ1 receptor radiotracer with superior imaging properties. The pure enantiomers of unlabeled compounds (S)- and (R)-1 and the corresponding iodonium ylide precursors were synthesized and characterized. The two enantiomers (S)-1 and (R)-1 exhibited comparable high affinity for σ1 receptors and selectivity over σ2 receptors. The Ca2+ fluorescence assay indicated that (R)-1 behaved as an antagonist and (S)-1 as an agonist for σ1 receptors. The 18F-labeled enantiomers (S)- and (R)-[18F]1 were obtained in > 99% enantiomeric purity from the corresponding enantiopure iodonium ylide precursors with radiochemical yield of 24.4% ± 2.6% and molar activity of 86-214 GBq/µmol. In ICR mice both (S)- and (R)-[18F]1 displayed comparable high brain uptake, brain-to-blood ratio, in vivo stability and binding specificity in the brain and peripheral organs. In micro-positron emission tomography (PET) imaging studies in rats, (S)-[18F]1 exhibited faster clearance from the brain than (R)-[18F]1, indicating different brain kinetics of the two enantiomers. Both (S)- and (R)-[18F]1 warrant further evaluation in primates to translate a single enantiomer with more suitable kinetics for imaging the σ1 receptors in humans.
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