A Proof-of-Concept Study on the Theranostic Potential of 177 Lu-labeled Biocompatible Covalent Polymer Nanoparticles for Cancer Targeted Radionuclide Therapy.

Theranostic nanomedicine combined bioimaging and therapy probably rises more helpful and interesting opportunities for personalized medicine. In this work, 177 Lu radiolabeling and surface PEGylation of biocompatible covalent polymer nanoparticles (CPNs) have generated a new theranostic nanoformulation (177 Lu-DOTA-PEG-CPNs) for targeted diagnosis and treatment of breast cancer. The in vitro anticancer investigations demonstrate that 177 Lu-DOTA-PEG-CPNs possess excellent bonding capacity with breast cancer cells (4T1), inhibiting the cell viability, leading to cell apoptosis, arresting the cell cycle, and upregulating the reactive oxygen species (ROS), which can be attributed to the good targeting ability of the nanocarrier and the strong relative biological effect of the radionuclide labelled compound. Single photon emission computed tomography/ computed tomography (SPECT/CT) imaging and in vivo biodistribution based on 177 Lu-DOTA-PEG-CPNs reveal that notable radioactivity accumulation at tumor site in murine 4T1 models with both intravenous and intratumoral administration of the prepared radiotracer. Significant tumor inhibition has been observed in mice treated with 177 Lu-DOTA-PEG-CPNs, of which the median survival was highly extended. More strikingly, 50 % of mice intratumorally injected with 177 Lu-DOTA-PEG-CPNs was cured and showed no tumor recurrence within 90 days. The outcome of this work can provide new hints for traditional nanomedicines and promote clinical translation of 177 Lu radiolabeled compounds efficiently.

Biocompatible conjugated polymer nanoparticles labeled with 225Ac for tumor endoradiotherapy.

Recently, endoradiotherapy based on actinium-225 (225Ac) has attracted increasing attention, which is due to its α particles can generate maximal damage to cancer cells while minimizing unnecessary radiation effects on healthy tissues. Herein, 111In/225Ac-radiolabeled conjugated polymer nanoparticles (CPNs) coated with amphiphilic polymer DSPE-PEG-DOTA have been developed as a new injectable nano-radiopharmaceuticals for cancer endoradiotherapy under the guidance of nuclear imaging. Single photon emission computed tomography/computed tomography (SPECT/CT) using 111In-DOTA-PEG-CPNs as nano probe indicates a prolonged retention of radiolabeled nanocarriers, which was consistent with the in vivo biodistribution examined by direct radiometry analysis. Significant inhibition of tumor growth has been observed in murine 4T1 models treated with 225Ac-DOTA-PEG-CPNs when compared to mice treated with PBS or DOTA-PEG-CPNs. The 225Ac-DOTA-PEG-CPNs group experienced no single death within 24 days with the median survival considerably extended to 35 days, while all the mice treated with PBS or DOTA-PEG-CPNs died at 20 days post injection. Additionally, the histopathology studies demonstrated no obvious side effects on healthy tissues after treatment with 225Ac-DOTA-PEG-CPNs. All these results reveal that the new 225Ac-labeled DOTA-PEG-CPNs is promising as paradigm for endoradiotherapy.

The disulfidptosis-related signature predicts prognosis and immune features in glioma patients.

Glioma is the most common primary malignant tumor in the central nervous system. Disulfidptosis is a recently identified programmed cell death in tumor cells overexpressing SLC7A11 under glucose starvation. Clinical prognostic significance of disulfidptosis has been reported in several tumors, and in this study, we explored the correlation of disulfidptosis with clinical prognosis, immune cell infiltration, and immunotherapy response in glioma. A total of 1592 glioma patients were included in this study, including 691 glioma patients from The Cancer Genomic Atlas (TCGA), 300 patients with from the Chinese Glioma Genomic Atlas (CGGA) array, 325 patients from CGGA sequencing, and 276 patients from Gene Expression Omnibus (GEO) GSE16011. R software (V4.2.2) and several R packages were applied to develop the risk score model and correlation calculation and visualization. Three disulfidptosis-related genes, LRPPRC, RPN1, and GYS1, were screened out and applied to establish the risk score model. Low-risk patients exhibit favorable prognosis, and the disulfidptosis-related signature significantly correlated with clinicopathological properties, molecular subtypes, and immunosuppressive microenvironment of glioma patients. We developed a disulfidptosis-related risk model to predict the prognosis and immune features in glioma patients, and this risk model may be applied as an independent prognostic factor for glioma.

Multimodal Imaging-Guided Strategy for Developing 177Lu-Labeled Metal-Organic Framework Nanomedicine with Potential in Cancer Therapy.

Nano-metal-organic frameworks (nano-MOFs) labeled with radionuclides have shown great potential in the anticancer field. In this work, we proposed to combine fluorescence imaging (FI) with nuclear imaging to systematically evaluate the tumor inhibition of new nanomedicines from living cancer cells to the whole body, guiding the design and application of a high-performance anticancer radiopharmaceutical to glioma. An Fe-based nano-MOF vector, MIL-101(Fe)/PEG-FA, was decorated with fluorescent sulfo-cyanine7 (Cy7) to investigate the binding affinity of the targeting nanocarriers toward glioma cells in vitro, as well as possible administration modes for in vivo cancer therapy. Then, lutetium-177 (177Lu)-labeled MIL-101(Fe)/PEG-FA was prepared for high-sensitive imaging and targeted radiotherapy of glioma in vivo. It has been demonstrated that the obtained 177Lu-labeled MIL-101(Fe)/PEG-FA can work as a complementary probe to rectify the cancer binding affinity of the prepared nanocarrier given by fluorescence imaging, providing more precise biodistribution information. Besides, 177Lu-labeled MIL-101(Fe)/PEG-FA has excellent antitumor effect, leading to cell proliferation inhibition, upregulation of intracellular reactive oxygen species, tumor growth suppression, and immune response-related protein and cytokine upregulation. This work reveals that optical imaging and nuclear imaging can work complementarily as multimodal imaging in the design and evaluation of anticancer nanomedicine, offering a MIL-101(Fe)/PEG-FA-based pharmaceutical with potential in tumor endoradiotherapy.

Two different initial treatment regimens of Conbercept in diabetic macular edema: 12-month results from a multicenter randomized controlled study.

BACKGROUND: The optimal treatment regimen for diabetic macular edema (DME) and predictors for its treatment`s outcome need emerging evidence but currently poorly studied. METHODS: A prospective, multicenter, open label randomized controlled study among adult patients with DME was conducted. Eyes were randomized to three or six doses initial Conbercept treatments. Additional injections were suggested pro re nata (PRN) over 12 months. Optical coherence tomography angiography (OCTA) was adopted to quantify the macular vessel density. Visual acuity gain and anatomical improvement and their associated factors were evaluated by multivariable linear regression. RESULTS: 41 patients with 59 eyes participated in current study. Patients in both 3 + PRN (n = 32 eyes) or 6 + PRN (n = 27 eyes) treatments experienced similar best-corrected visual acuity (BCVA) gain and anatomical improvement, including the central macular thickness, foveal avascular aone (FAZ) and the retinal vessel density. Over 12 months, eyes in the 6 + PRN group received better changes of the deep capillary plexus (2.53 ± 5.45%). In multivariate linear regression, the age significantly affected visual outcome in 3 + PRN group (ß = -0.014, P = 0.028), while the initial CMT (ß = -0.001, P = 0.022) and FAZ area (ß = -0.946, P = 0.007) associated with visual outcome in 6 + PRN group. Furthermore, the duration of diabetes exhibited significant results on CMT among 3 + PRN group (ß= -7.516, P = 0.04). CONCLUSIONS: Both 3 + and 6 + initial treatment regimens of Conbercept loading dose achieved parallel anatomical and functional visual improvement, while 6 + group had a trend of better treatment outcome. Older age, higher initial CMT and longer duration of diabetes might influence the clinical outcomes over 12 months from baseline.

Explainable ensemble machine learning model for prediction of 28-day mortality risk in patients with sepsis-associated acute kidney injury.

Background: Sepsis-associated acute kidney injury (S-AKI) is a major contributor to mortality in intensive care units (ICU). Early prediction of mortality risk is crucial to enhance prognosis and optimize clinical decisions. This study aims to develop a 28-day mortality risk prediction model for S-AKI utilizing an explainable ensemble machine learning (ML) algorithm. Methods: This study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.0) database to gather information on patients with S-AKI. Univariate regression, correlation analysis and Boruta were combined for feature selection. To construct the four ML models, hyperparameters were tuned via random search and five-fold cross-validation. To evaluate the performance of all models, ROC, K-S, and LIFT curves were used. The discrimination of ML models and traditional scoring systems was compared using area under the receiver operating characteristic curve (AUC). Additionally, the SHapley Additive exPlanation (SHAP) was utilized to interpret the ML model and identify essential variables. To investigate the relationship between the top nine continuous variables and the risk of 28-day mortality. COX regression-restricted cubic splines were utilized while controlling for age and comorbidities. Results: The study analyzed data from 9,158 patients with S-AKI, dividing them into a 28-day mortality group of 1,940 and a survival group of 7,578. The results showed that XGBoost was the best performing model of the four ML models with AUC of 0.873. All models outperformed APS-III 0.713 and SAPS-II 0.681. The K-S and LIFT curves indicated XGBoost as the most effective predictor for 28-day mortality risk. The model's performance was evaluated using ROCpr curves, calibration curves, accuracy, precision, and F1 scores. SHAP force plots were utilized to interpret and visualize the personalized predictive power of the 28-day mortality risk model. Additionally, COX regression restricted cubic splines revealed an interesting non-linear relationship between the top nine variables and 28-day mortality. Conclusion: The use of ensemble ML models has shown to be more effective than the LR model and conventional scoring systems in predicting 28-day mortality risk in S-AKI patients. By visualizing the XGBoost model with the best predictive performance, clinicians are able to identify high-risk patients early on and improve prognosis.

A Smart Benzothiazole-Based Conjugated Polymer Nanoplatform with Multistimuli Response for Enhanced Synergistic Chemo-Photothermal Cancer Therapy.

The combination of chemotherapy and phototherapy has received tremendous attention in multimodal cancer therapy. However, satisfactory therapeutic outcomes of chemo-photothermal therapy (chemo-PTT) still remain challenging. Herein, a biocompatible smart nanoplatform based on benzothiazole-linked conjugated polymer nanoparticles (CPNs) is rationally designed, for effectively loading doxorubicin (DOX) and Mo-based polyoxometalate (POM) through both dynamic chemical bond and intermolecular interactions, with an expectation to obtain new anticancer drugs with multiple stimulated responses to the tumor microenvironment (TME) and external laser irradiation. Controlled drug release of DOX from the obtained nanoformulation (CPNs-DOX-PEG-cRGD-BSA@POM) triggered by both endogenous stimulations (GSH and low pH) and exogenous laser irradiation has been well demonstrated by pharmacodynamics investigations. More intriguingly, incorporating POM into the nanoplatform not only enables the nanomedicine to achieve mild hyperthermia but also makes it exhibit self-assembly behavior in acidic TME, producing enhanced tumor retention. Benefiting from the versatile functions, the prepared CPNs-DOX-PEG-cRGD-BSA@POM exhibited excellent tumor targeting and therapeutic effects in murine xenografted models, showing great potential in practical cancer therapy.

Targeted Alpha Therapy of Glioma Using 211At-Labeled Heterodimeric Peptide Targeting Both VEGFR and Integrins.

Targeted radionuclide therapy based on α-emitters plays an increasingly important role in cancer treatment. In this study, we proposed to apply a heterodimeric peptide (iRGD-C6-lys-C6-DA7R) targeting both VEGFR and integrins as a new vector for 211At radiolabeling to obtain high-performance radiopharmaceuticals with potential in targeted alpha therapy (TAT). An astatinated peptide, iRGD-C6-lys(211At-ATE)-C6-DA7R, was prepared with a radiochemical yield of ∼45% and high radiochemical purity of >95% via an electrophilic radioastatodestannylation reaction. iRGD-C6-lys(211At-ATE)-C6-DA7R showed good stability in vitro and high binding ability to U87MG (glioma) cells. Systematic in vitro antitumor investigations involving cytotoxicity, apoptosis, distribution of the cell cycle, and reactive oxygen species (ROS) clearly demonstrated that 211At-labeled heterodimeric peptides could significantly inhibit cell viability, induce cell apoptosis, arrest the cell cycle in G2/M phase, and increase intracellular ROS levels in a dose-dependent manner. Biodistribution revealed that iRGD-C6-lys(211At-ATE)-C6-DA7R had rapid tumor accumulation and fast normal tissue/organ clearance, which was mainly excreted through the kidneys. Moreover, in vivo therapeutic evaluation indicated that iRGD-C6-lys(211At-ATE)-C6-DA7R was able to obviously inhibit tumor growth and prolong the survival of mice bearing glioma xenografts without notable toxicity to normal organs. All these results suggest that TAT mediated by iRGD-C6-lys(211At-ATE)-C6-DA7R can provide an effective and promising strategy for the treatment of glioma and some other tumors.

Superior Radiation Resistance of ZrO2-Modified W Composites.

The microstructure and mechanical properties of pure W, sintered and swaged W-1.5ZrO2 composites after 1.5 × 1015 Au+/cm2 radiation at room temperature were characterized to investigate the impact of the ZrO2 phase on the irradiation resistance mechanism of tungsten materials. It can be concluded that the ZrO2 phase near the surface consists of two irradiation damage layers, including an amorphous layer and polycrystallization regions after radiation. With the addition of the ZrO2 phase, the total density and average size of dislocation loops, obviously, decrease, attributed to the reason that many more glissile 1/2<111> loops migrate to annihilate preferentially at precipitate interfaces with a higher sink strength of 7.8 × 1014 m−2. The swaged W-1.5ZrO2 alloys have a high enough density of precipitate interfaces and grain boundaries to absorb large numbers of irradiated dislocations. This leads to the smallest irradiation hardening change in hardness of 4.52 Gpa, which is far superior to pure W materials. This work has a collection of experiments and conclusions that are of crucial importance to the materials and nuclear communities.

PET imaging of VEGFR and integrins in glioma tumor xenografts using 89Zr labelled heterodimeric peptide.

Vascular endothelial growth factor receptor (VEGFR) and integrin αv are over-expressed in angiogenesis of variety malignant tumors with key roles in angiogenesis, and have been proven as valuable targets for cancer imaging and treatment. In this study, a heterodimeric peptide targeting VEGFR and integrin was designed, and radiolabeled with zirconium-89 (89Zr) for PET imaging of glioma. 89Zr-DFO-heterodimeric peptide, a the newly developed probe, was prepared with radiochemical yield of 88.7 ± 2.4%. Targeted binding capability of 89Zr-DFO-heterodimeric peptide towards U87MG cells was investigated in murine glioma xenograft models, which shows that the designed probe has good binding ability to both targeting sites. Biodistribution indicated that kidney metabolism is the main pathway and tumor uptake of 89Zr-DFO-heterodimeric peptide reached the peak of 0.62 ± 0.10% ID/g . U87MG xenograft could be clearly visualized by microPET/CT imaging through 1 to 3 h post-injection of 89Zr-DFO-heterodimeric peptide. Importantly, the tumor radiouptake was significantly reduced after blocking, and the imaging effect of this radioactive compound was more obvious than that of monomeric peptide probes. 89Zr-DFO-heterodimeric peptide has been demonstrated to show potential as a new radiopharmaceutical probe towards glioma, and multi-target probes do have advantages in tumor imaging.

In Vitro Anticancer Ability of Nano Fluorescent 111 In-MIL-68/PEG-FA on Hela Cells.

In past decades, nanoscale metal-organic frameworks (NMOFs) have drawn more and more attention in multimodal imaging and targeting therapy of various malignant cancers. Here, we proposed to dope 111 In into fluorescent In-based NMOFs (In-MIL-68-NH2 ), with an attempt to prepare a new nanomedicine with great anticancer potential. As a proof of concept, the obtained NMOF (In-MIL-68/PEG-FA) with targeting motifs is able to act as a fluorescent probe to achieve Hela cell imaging. Moreover, the Auger electron emitter 111 In built in corresponding radioactive NMOF (111 In-MIL-68/PEG-FA) can bring clear damage to cancer cells, leading to a high cell killing rate of 59.3 % within 48 h. In addition, the cell cycle presented a significant dose-dependent G2/M inhibiting mode, which indicates that 111 In-MIL-68/PEG-FA has the ability to facilitate the cancer cells to enter apoptotic program. This work demonstrated the potential of 111 In-labelled NMOFs in specific killings of cancer cells, providing a new approach to develop nanomedicines with theranostic function.

In vitro and in vivo evaluation of 211At-labeled fibroblast activation protein inhibitor for glioma treatment.

Glioma is the most common primary intracranial tumor without effective treatment. Positron emission tomography tracers labeled with 68Ga targeting fibroblast activation protein (FAP) have shown favorable characteristics in the diagnosis of glioma. However, to the best of our knowledge, FAP-targeted endoradiotherapy has never been explored in glioma. Hence, in this study, we investigated the therapeutic effect of 211At-labeled fibroblast activation protein inhibitor (FAPI) for glioma in vitro and in vivo. By astatodestannylation reaction, we prepared 211At-FAPI-04 with a radiochemical yield of 45 ± 6.7% and radiochemical purity of 98%. With good stability in vitro, 211At-FAPI-04 showed fast and specific binding to FAP-positive U87MG cells, and could significantly reduce the cell viability, arrested cell cycle at G2/M phase and suppressed cell proliferative efficacy. Biodistribution studies revealed that 6-fold higher accumulation in tumor sites was achieved by intratumoral injection in comparison with intravenous injection. In U87MG xenografts, 211At-FAPI-04 obviously suppressed the tumor growth and prolonged the median survival in a dose-dependent manner without obvious toxicity to normal organs. In addition, reduced proliferation and increased apoptosis were also observed after 211At-FAPI-04 treatment. All these results suggest that targeted alpha-particle therapy (TAT) mediated by 211At-FAPI-04 can provide an effective and promising strategy for the treatment of glioma.

Effect of Al Concentration on Microstructure and Properties of AlNbTiZr Medium-Entropy Alloy Coatings.

The AlNbTiZr medium-entropy alloy (MEA) coatings with different Al contents were prepared on N36 zirconium alloy substrates by RF magnetron co-sputtering. The morphology, microstructure, mechanical properties, surface wettability and corrosion resistance of the AlNbTiZr MEA coatings were studied to evaluate the surface protection behavior of zirconium alloy cladding under operation conditions of a pressurized water reactor. The results showed that all the coatings were composite structures with amorphous and bcc-structured nanocrystals. With the increase of Al content, both the elastic modulus and hardness decreased first and then increased. The hydrophobicity of the coatings was enhanced compared with that of the substrate. The 10.2 at.% Al AlNbTiZr coating had the best corrosion resistance and the minimum oxygen penetration depth, which originated from the formation of a denser oxide layer consisting of Nb2Zr6O17 and ZrO2. This study provides an improved idea for the design and development of Al-containing MEA coating materials for accident tolerant fuel.

Frequency of and risk factors for intensive care unit-acquired sacrum pressure injuries in critically ill patients: A multicenter cross-sectional study in China.

RATIONALE AIMS AND OBJECTIVES: Hospital-acquired pressure injuries (HAPI) prolong hospital stays and are an important health problem worldwide. The aim of this study was to assess the frequency of and risk factors for intensive care unit (ICU)-acquired pressure injuries (IAPI) on the sacrum in critically ill patients in China. METHODS: We performed a multicenter, cross-sectional survey of IAPI on the sacrum in 23 adult ICUs in 19 hospitals in China. Data for 421 critically ill patients were collected on December 13, 2019, and January 13, 2020, including patient characteristics, physiological, and clinical information. Logistic regression was used to analyze the risk factors for IAPI on the sacrum in the ICU. RESULTS: Forty-one patients presented sacrum pressure injuries in the ICU, with a frequency of 9.74%. Risk factors that significantly increased the risk of IAPI on the sacrum were lower body mass index (BMI, odds ratio [OR] = 1.115, confidence interval [CI]: 1.011-1.229, P = .029), chronic obstructive pulmonary disease (COPD, OR = 3.183, CI: 1.261-8.037, P = .014), multiple organ dysfunction syndrome (MODS, OR = 2.670, CI: 1.031-6.903, P = .043), and a lower Braden risk score (OR = 1.409, CI: 1.197-1.659, P < .001). CONCLUSION: Lower BMI, COPD, MODS, and lower Braden risk score are independent risk factors for sacrum IAPI in China.

Synthesis and Preliminary Evaluation of 131I-Labeled FAPI Tracers for Cancer Theranostics.

As an excellent target for cancer theranostics, fibroblast activation protein (FAP) has become an attractive focus in cancer research. A class of FAP inhibitors (FAPIs) with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold were developed, which displayed nanomolar affinity and high selectivity. Compared with 90Y, 177Lu, 225Ac, and 188Re, 211At seems to be more favored as a therapeutic candidate for FAPI tracers which have fast washout and short retention in tumor sites. Thus, the current study reported the synthesis of two FAPI precursors for 211At and 131I labeling and the preliminary evaluation of 131I-labeled FAPI analogues for cancer theranostics. FAPI variants with stannyl precursors were successfully synthesized and labeled with 131I using a radioiododestannylation reaction. Two radioactive tracers were obtained with high radiochemical purity over 99% and good radiochemical yields of 58.2 ± 1.78 and 59.5 ± 4.44% for 131I-FAPI-02 and 131I-FAPI-04, respectively. Both tracers showed high specific binding to U87MG cells in comparison with little binding to MCF-7 cells. Compared to 131I-FAPI-02, 131I-FAPI-04 exhibited higher affinity, more intracellular uptake, and longer retention time in vitro. Biodistribution studies revealed that both tracers were mainly excreted through the kidneys as well as the hepatobiliary pathway due to their high lipophilicity. In addition, higher accumulation, longer dwell time, and increased tumor-to-organ ratios were achieved by 131I-FAPI-04, which was clearly demonstrated by SPECT/CT imaging. Furthermore, intratumor injection of 131I-FAPI-04 significantly suppressed the tumor growth in U87MG xenograft mice without significant toxicity observed. The above results implied that FAP-targeted alpha endoradiotherapy (specific to 211At) should be used to treat tumors in the near future, considering the chemical similarity between iodine and astatine can ensure the labeling of the latter onto the designed FAPIs.

Simple and efficient method for producing high radionuclidic purity 111In using enriched 112Cd target.

In this work, a simple and efficient method for producing high radionuclidic purity 111In from an enriched 112Cd target was developed. The enriched 112Cd metal target formed by cyanide-free electroplating was bombarded with protons of 21 MeV in a CS-30 cyclotron. Then, we explored a purification scheme using CL-P204 cation exchange resin wherein 98% of the 111In in the bombarded target could be extracted in less than 1 h. The purified 111In in the form of [111In]In-chloride had a high radionuclidic purity (99.9%) and a low impurity concentration (<1.2 ppm). The yield of 111In via the reaction of 112Cd (p, 2n) 111In was measured to be 222 ± 5 MBq/µA∙h. In addition, a chemical procedure for collecting the unreacted 112Cd at a recovery rate of 96.6% was explored.

Production of 98Tc with high isotopic purity.

In this work, technetium-98 (98Tc) was prepared with high isotopic purity via the nuclear reaction 98Mo (p, n) 98Tc for the first time. An enriched 98Mo metal target formed by spark plasma sintering was bombarded with 9.4 MeV protons in a CS-30 cyclotron. A microgram amount of 98Tc with 99.18% isotopic purity was separated from the irradiated target by anion exchange chromatography. Additionally, a chemical procedure for recovering the enriched 98Mo with a 97% recovery rate was developed.

Effect of kallikrein on microcirculation of rats with pancreatic ischemia reperfusion injury (IRI).

The common pathway for pancreatitis onset is pancreatic ischemia reperfusion injury (IRI), which plays an especially significant role in the evolution process from acute edematous pancreatitis (AP) towards severe acute pancreatitis (SAP). This study explored the effect of Kallikrein (PK) on pancreatic ischemia reperfusion injury (IRI). Male Wistar rats were taken as study objects, and a SAP -IRI combined model was established through retrograde infusion of 5% sodium taurocholate in biliopancreatic duct combining 30 min splenic artery clipping; drug intervention was carried out by pumping PK into rat caudal vein. Pancreatic microcirculation blood flow, pancreatic micro vascular permeability, hemorheological change and levels of adherence factors CD18 and CD54 were determined respectively. PK can obviously improve pancreatic microcirculation blood flow volume and velocity of IRI rats and expand arteriole; expand diameter of pancreatic blood capillary so that perfusion state tends to be stable; decrease pancreatic micro vascular permeability, reduce rat whole blood viscosity, erythrocyte deformation index and rigidity index; SAP-IRI combination reduces expression levels of white cell adhesion factor CD18 and vascular endothelial cell adhesion cell CD54 in rats. In conclusion, PK is an effective method of improving SAP pancreatic IRI microcirculation.

Sorption of selenite on Tamusu clay in simulated groundwater with high salinity under aerobic/anaerobic conditions.

The sorption behavior of selenite onto the Tamusu clay from a preselected high-level radioactive waste disposal site in Inner Mongolia, China, was first investigated in simulated groundwater with high salinity by batch sorption experiments under aerobic/anaerobic conditions. The results demonstrated that the Kd values rapidly decreased and then remained steady in the pH range of 2.0-8.0. However, selenite sorption was promoted when pH exceeded 8.0, which might be attributed to the coprecipitation between Ca2+ and SeO32-. Besides, the change trend of the Kd values as functions of various parameters was not affected by oxygen. The sorption kinetics and isotherms could be well fitted by the pseudo-second-order kinetic model and the Freundlich model for both aerobic and anaerobic conditions, and the calculated thermodynamic parameters (△G and △H) suggested that the selenite sorption process was a spontaneous and endothermic process. Additionally, the XPS results revealed that Se(IV) could be reduced to Se (0) only in anaerobic conditions and that the different amounts of Fe on the clay surface led to the discrepancy of the Se(IV) Kd values under aerobic and anaerobic conditions even in high-salt simulated groundwater. Overall, our findings in this study are significant in regards to the retardation of selenite on the host rock under high salinity conditions.

A radiopharmaceutical [89Zr]Zr-DFO-nimotuzumab for immunoPET with epidermal growth factor receptor expression in vivo.

INTRODUCTION: The potential of the positron-emitting zirconium-89 (89Zr) (t1/2 = 78.4 h) has been recently reported for immune positron emission tomography (immunoPET) radioimmunoconjugates design. In our work, we explored the optimized preparation of [89Zr]Zr-DFO-nimotuzumab, and evaluated 89Zr-labeled monoclonal antibody (mAb) construct for targeted imaging of epidermal growth factor receptor (EGFR) overexpressed in glioma. METHODS: To optimize the radiolabeling efficiency of 89Zr with DFO-nimotuzumab, multiple immunoconjugates and radiolabeling were performed. Radiolabeling yield, radiochemical purity, stability, and activity assay were investigated to characterize [89Zr]Zr-DFO-nimotuzumab for chemical and biological integrity. The in vivo behavior of this tracer was studied in mice bearing subcutaneous U87MG (EGFR-positive) tumors received a 3.5 ±â€¯0.2 MBq/dose using PET/CT imaging. One group mice bearing subcutaneous U87MG (EGFR-positive) tumors received [89Zr]Zr-DFO-nimotuzumab (3.5 ±â€¯0.2 MBq, ~3 µg) (nonblocking) for immunoPET; the other group had 30 µg predose (blocking) of cold nimotuzumab 24 h prior to [89Zr]Zr-DFO-nimotuzumab. RESULTS: [89Zr]Zr-DFO-nimotuzumab was prepared with high radiochemical yield (>90%), radiochemical purity (>99%), and specific activity (115 ±â€¯0.8 MBq/mg). In vitro validation showed that [89Zr]Zr-DFO-nimotuzumab had an initial immunoreactive fraction of 0.99 ±â€¯0.05 and remained active for up to 5 days. A biodistribution study revealed excellent stability of [89Zr]Zr-DFO-nimotuzumab in vivo compared with 89Zr as a bone seeker. High uptake in the liver and heart and modest penetration in the brain were observed, with no significant accumulation of activity in other organs. ImmunoPET studies also indicated prominent image contrast that remarkably high uptake up to ~20%ID/g for nonblocking and ~2%ID/g for blocking in tumor between 12 and 120 h after administration. CONCLUSION: These studies developed a radiopharmaceutical [89Zr]Zr-DFO-nimotuzumab with optimized synthesis. The potential utility of [89Zr]Zr-DFO-nimotuzumab in assessing EGFR status in glioma was demonstrated in this study.