AIM: To investigate the effects of the WWOX gene on the human hepatic carcinoma cell line SMMC-7721. METHODS: Full-length WWOX cDNA was amplified from normal human liver tissues. Full-length cDNA was subcloned into pE...AIM: To investigate the effects of the WWOX gene on the human hepatic carcinoma cell line SMMC-7721. METHODS: Full-length WWOX cDNA was amplified from normal human liver tissues. Full-length cDNA was subcloned into pEGFP-N1, a eukaryotic expression vector. After introduction of the WWOX gene into cancer cells using liposomes, the WWOX protein level in the cells was detected through Western blotting. Cell growth rates were assessed by methyl thiazolyl tetrazolium (MTT) and colony formation assays. Cell cycle progression and cell apoptosis were measured by flow cytometry. The phosphorylated protein kinase B (AKT) and activated fragments of caspase-9 and caspase-3 were examined by Western blotting analysis. RESULTS: WWOX significantly inhibited cell proliferation, as evaluated by the MTT and colony formation assays. Cells transfected with WWOX showed significantly higher apoptosis ratios when compared with cells transfected with a mock plasmid, and overexpression of WWOX delayed cell cycle progression from G1 to S phase, as measured by flow cytometry. An increase in apoptosis was also indicated by a remarkable activation of caspase-9 and caspase-3 and a dephosphorylation of AKT (Thr308 and Ser473) measured with Western blotting analysis. CONCLUSION: Overexpression of WWOX induces apoptosis and inhibits proliferation of the human hepatic carcinoma cell line SMMC-7721.展开更多
A competitive indirect time-resolved fluoroimmunoassay(TRFIA) was developed for detection of zearalenone(ZEN) in cereals,in which ZEN conjugated to bovine serum albumin(BSA) is used as solid-phase antigen.A competitiv...A competitive indirect time-resolved fluoroimmunoassay(TRFIA) was developed for detection of zearalenone(ZEN) in cereals,in which ZEN conjugated to bovine serum albumin(BSA) is used as solid-phase antigen.A competitive indirect TRFIA was conducted by simultaneously incubating ZEN in standard or extracted samples with anti-ZEN monoclonal antibody over ZEN-BSA coated plates,and then determining the bound ZEN monoclonal antibody with goat anti-mouse europium conjugate.Samples were extracted with methanol/water...展开更多
A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in condi...A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in conditions of 0.1 mg SnCl2.2H2O at pH 6.0 and 99TcmO4? in aqueous solution for 20 min at room temperature. The labeling yield and radiochemical purity of 99Tcm-PIDP are both higher than 95%. The biodistribution results show that the bone uptake is up to 8.47% ID/g which is the maximum of bone uptake at 30 min after injection of 99Tcm-PIDP in mice. The pharmacokinetic parameters can be estimated from the exponential equation of C=59.565e-11.307t+2.069e-1.211t. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-PIDP. The results indicate that 99Tcm-PIDP has highly selective uptake in the skeletal and low uptake, rapid clearance in soft tissues, so it would be a potential novel bone imaging agent.展开更多
Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibi...Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.展开更多
Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of t...Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value(SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer(CRC) in mice. Methods: Colorectal liver metastases(CRLM) xenograft models were established by injecting tumor cells(LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. ^(18)F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^(18)F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the ^(18)F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1 α(HIF-1 α) and serum starvation-induced glucose transporter 1(GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, ^(18)F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between ^(18)F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ^(18)F-FMISO SUVmax ratio and HIF-1 α or GLUT-1 expression in tumor-bearing tissues. Conclusions: ^(18)F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.展开更多
Asialoglycoprotein receptor(ASGP-R)is a hepatic membrane receptor that uniquely exists on the surface of mammalian hepatocytes,and has been used as target of liver functional imaging agents for many years.We labeled t...Asialoglycoprotein receptor(ASGP-R)is a hepatic membrane receptor that uniquely exists on the surface of mammalian hepatocytes,and has been used as target of liver functional imaging agents for many years.We labeled the Galactosyl-neoglycoalbumin(NGA)with 18F to get a PET molecular probe 18F-FB-NGA and evaluated its ability as a liver functional PET imaging agent.The 18F-FB-NGA was prepared with NGA by conjugation with Nsuccinimidyl-4-18F-fluorobenzoate(18F-SFB)and purified with PD-10 desalting column.The radiolabeling yield and radiochemical purity of 18F-FB-NGA were determined by radio-HPLC.Starting with 18F-F–,the total time for 18F-FB-NGA was about 120±10 min.The decay-corrected radiochemical yield is about 25–30%.The radiochemical purity of purified 18F-FB-NGA was more than 98%.Labeled with 185–1850 MBq 18F-SFB,the specific activity of 18F-FBNGA was estimated to be 7.83–78.3 TBq/mmol.Biodistribution of 18F-FB-NGA in normal mice was investigated after injection through the tail vein.The results showed that the liver accumulated 39.47±3.42 and 12.12±6.11%ID/g at 10 and 30 min after injection,respectively.Dynamic MicroPET images in mice were acquired with and without block after injection of the radiotracer,respectively.High liver activity accumulation was observed at 5 min after injection in normal group.On the contrary,the liver accumulation was significantly lower after block,indicating the specific binding to ASGP-R.18F-FB-NGA is probably a potential PET liver imaging agent.展开更多
99mTc-HMIBP, a new bone-imaging agent, was prepared by the reduction of 99mTc-pertechnetate in the presence of SnCl2?2H2O. The effects of the amounts of SnCl2?2H2O and HMIBP and the pH value on the labeling yield and ...99mTc-HMIBP, a new bone-imaging agent, was prepared by the reduction of 99mTc-pertechnetate in the presence of SnCl2?2H2O. The effects of the amounts of SnCl2?2H2O and HMIBP and the pH value on the labeling yield and radiochemical purity of 99mTc-HMIBP were investigated. When the amounts of SnCl2?2H2O and HMIBP were more than 10 μg and 2.5 mg, respectively, the pH value was between 2 and 7, and the labeling reaction contin- ued for 10 min, both labeling yield and radiochemical purity of 99mTc-HMIBP were more than 90%. The biodistribu- tion in rats and bone scan in rabbits were also studied. The results showed that the bone uptake is up to 7.94%ID/g at 30 min after injection of 99mTc-HMIBP, bone-to-muscle and bone-to-blood uptake ratios were 20.89 and 16.89, re- spectively. The clear bone image was obtained at 120 min after injection of 99mTc-HMIBP and clearance in soft tissue was visible. All of the above-mentioned results suggested that 99mTc-HMIBP may be a potential bone-imaging agent.展开更多
Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correl...Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,^(68)Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer ^(68)Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.展开更多
Background:Positron emission tomography (PET) imaging is a non-invasive method to visualize and quantify the tumor microenvironment.This study aimed to explore the feasibility of ^(18)F-AIF-NOTA-E[PEG_(4-c)(RGDfk)]_(2...Background:Positron emission tomography (PET) imaging is a non-invasive method to visualize and quantify the tumor microenvironment.This study aimed to explore the feasibility of ^(18)F-AIF-NOTA-E[PEG_(4-c)(RGDfk)]_(2) (denoted as ^(18)F-RGD) PET quantitative parameters to distinguish the angiogenesis in colorectal cancer (CRC) mice which has different metastatic potential.Methods:Twenty Lo Vo and twenty LS174T of CRC liver metastases animal models were established by implantation of human CRC cell lines via intrasplenic injection.Radiotracer-based micro-PET imaging of animal model was performed and the uptake of ^(18)F-RGD tracer in the tumor tissues was quantified as tumor-to-liver maximum or mean standardized uptake value (SUVmax or SUVmean) ratio.Pearson correlation was used to analyze the relationship between radioactive parameters and tumor markers.Results:The SUVmax and SUVmean ratios of Lo Vo model were significantly higher than those of LS174T in both liver metastasis and primary tumor lesions (P<0.05).A significant difference was observed in both vascular endothelial growth factor (VEGF) and Ki67 expressions between Lo Vo and LS174T primary tumors (P<0.05).The tumor-to-liver SUVmax or SUVmean ratio of ^(18)F-RGD showed a moderate correlation with VEGF expression (r=0.5700,P=0.001 and r=0.6657,P<0.001,respectively),but the SUVmean ration showed a weak correlation with Ki67 expression (r=0.3706,P<0.05).The areas under the receiver operating characteristic (ROC) curves of ^(18)F-RGD SUVmean ratio,SUVmax ratio for differentiating Lo Vo from LS174T tumor were 0.801 and 0.759,respectively.Conclusions:The tumor-to-liver SUVmean ratio of ^(18)F-RGD was a promising image parameter for the process of monitoring tumor angiogenesis in CRC xenograft mice model.展开更多
Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers pro...Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.展开更多
Eu-chelate were used to construct a two-site sandwich-type assay for pepsinogen Ⅰ (PGI) with time-resolved fluoroimmunoassay (TRFIA) as a detection technique. On the noncompetitive assay, captured monoclonal anti...Eu-chelate were used to construct a two-site sandwich-type assay for pepsinogen Ⅰ (PGI) with time-resolved fluoroimmunoassay (TRFIA) as a detection technique. On the noncompetitive assay, captured monoclonal antibodies (McAbs) coated on wells were directed against a specific antigenic site on the PGI. Another McAbs, called as labeling McAbs, were prepared with the Eu-chelate of N-(p-isothiocyanatobenzyl)-diethylenetriamine-N, N, N, N-tetraacetic acid and directed against a different antigenic site on the PGI. The fluorescence counts of bound Eu^3+ -McAbs were measured with the auto DELFIA1235 system. The PGI in sera from healthy volunteers were determined by PGI-TRFIA. The within-run and between-run CVs of the PGI-TRFIA were 1.9% and 4.7%, respectively, and the recovery rate was 102.65%. The assay had a detection limit of 0.05 μg· L^-1. The PGI-TRFIA provided a linear response from 3.5 to 328 μg· L^-1. The cross-reacting rate with pepsinogen Ⅱ was negligible. The linear correlation of PGI-TRFIA and radioimmunassay measurements resulted in a correlation coefficient of 0.977. The means of healthy volunteers were 154 ±43 μg·L^-1 for serum PGI. The availability of a highly sensitive, reliable, and convenient method for quantifying PGI will allow investigations into the possible diagnostic value of this analyte in various clinical conditions, including gastric carcinoma, duodenal ulcer, gastritis and severe atrophic gastritis.展开更多
Technetium-99m-labeled-5-{2-sulfanylethyl-[2-(2-sulfanylethylamino)acetyl]amino}-methyl-2′-deoxy- uridine (99mTc-ANMdU) was reported. The precursor ANMdU was synthesized by six-step reactions and all intermediates we...Technetium-99m-labeled-5-{2-sulfanylethyl-[2-(2-sulfanylethylamino)acetyl]amino}-methyl-2′-deoxy- uridine (99mTc-ANMdU) was reported. The precursor ANMdU was synthesized by six-step reactions and all intermediates were verified with MS and 1HNMR. Using SnCl2 as reducing agent, a labeling reaction was carried out at 100°C for 30 min. The radiochemical purity of the 99mTc-ANMdU was 96.68%. Partition coefficients were 0.92 and 0.70 at pH 7.0 and 7.4 of the phosphate buffer saline, respectively. Biodistribution of 99mTc-ANMdU in normal mice showed that the initial uptake of 99mTc-ANMdU in vivo and the clearance was rapid.展开更多
TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99Tc...TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99TcmO4 with SnCl2·2H2O in aqueous solution for 10 min at room temperature. Both labeling yield and radiochemical - purity of Tcm-TADP were more than 95%. The biodistribution in rats and bone scan in rabbits were also studied. The 99 uptake of organ was expressed as %ID/g. The results showed that the bone uptake is up to 17.17%ID/g which is the maximum of bone uptake at 30 min after injection of Tcm-TADP in rats, bone-to-muscle and bone-to-blood uptake 99 ratios were 61.32 and 13.21, respectively. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-TADP and clearance in soft tissue was visible. The preparation of 99Tcm-TADP was convenient and 99Tcm-TADP exhibited high uptake in bone, and it would be a potential new bone imaging agent.展开更多
The interleukin-11(IL-11)and the IL-11 receptorα-subunit(IL-11Rα)have been demonstrated to regulate the invasion and proliferation of tumor cells.Our study intends to evaluate a noninvasive imaging of IL-11Rαexpres...The interleukin-11(IL-11)and the IL-11 receptorα-subunit(IL-11Rα)have been demonstrated to regulate the invasion and proliferation of tumor cells.Our study intends to evaluate a noninvasive imaging of IL-11Rαexpression in breast tumors using near-infrared(NIR)fluorescent dye Cy7-labeled IL-11 mimic peptide CGRRAGGSC.This work evaluated the IL-11Rαexpression of breast tumor cells and the binding status of this peptide to IL-11Rαin vitro and in vivo by using Western blotting,immunofluorescence staining and near-infrared fluorescence imaging.Our biochemical study showed that IL-11Rαwas overexpressed in breast tumor cells(MCF-7).The cell-binding assay demonstrated specific binding of peptide CGRRAGGSC to MCF-7 cells in vitro.In vivo imaging results showed that NIR fluorescent signals of Cy7-CGRRAGGSC were selectively accumulated in tumor and metabolic organs.While in the blocking experiment,free CGRRAGGSC obviously blocked the concentration of the Cy7-CGRRAGGSC in the tumors.These results suggested that IL-11Rαmay be used as a potential target for noninvasive imaging in IL-11Rαoverexpressed tumors.Furthermore,the imaging agent of near-infrared fluorescent dye Cy7-labeled CGRRAGGSC is suitable for IL-11Rαexpression imaging study in vivo.展开更多
The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stan...The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stannous fluoride (SnF 2 ) as reducing agent. Biological characteristics of 99m Tc-PQQE include lipophilic and the charge properties were compared to 99m Tc-PQQ. The biodistributions of 99m Tc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99m Tc-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2β) results indicate that the residence time of 99m Tc-PQQE (203.92) in the body is twice as long as 99m Tc-PQQ (100.45). The uptake of 99m Tc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99m Tc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99m Tc-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that 99m Tc-PQQE has some specific targeting to the NMDA receptor.展开更多
To evaluate the clinical value of combined determination of serum PGⅠ, PGⅡ and GAS for early diag-nosis of gastric cancer, the serum levels of PGⅠ, PGⅡ and GAS in 190 healthy controls and 129 patients with gas-tri...To evaluate the clinical value of combined determination of serum PGⅠ, PGⅡ and GAS for early diag-nosis of gastric cancer, the serum levels of PGⅠ, PGⅡ and GAS in 190 healthy controls and 129 patients with gas-tric disorders were measured by RIA. The 129 patients include 68 cases of gastric cancer. The results showed that the serum levels of PGⅠ and PGⅠ/PGⅡ ratio in gastric cancer patients were obviously lower than those in healthy controls, while comparing with controls, the serum GAS levels were significantly higher. The diagnostic accuracy of the determinations for gastric cancer was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) levels of serum PGⅠ, PGⅠ/PGⅡ ratio and GAS were 0.833, 0.842 and 0.851, respec-tively. As serum PGⅠ or PGⅠ/PGⅡ ratio or GAS were combined, the sensitivity and specificity of determination for gastric cancer diagnosis were 94.2% and 73.4%, respectively. All these results indicated that the combined deter-mination of serum PGⅠ, PGⅡ and GAS levels may be used as a tool for primary screening of gastric cancer.展开更多
The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-memantine.The affinity and specificity...The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-memantine.The affinity and specificity were determined by radio-ligand receptor binding assay(RRA).Biodistribution in vivo in mice was performed.The results showed that ^(99)Tc^m-N-ethyl-N_2S_2-memantine bound to a single site on NMDA receptor with a K_d of 584.32 nmol/L and a B_(max)of 267.05 nmol/mg.A competitive analysis showed that such specific binding could be inhibited by specific inhibitors of NMDA receptor,such as ketamine and(+)-MK-801.The biodistribution exhibited rapid uptake and favorable retention in mice brains.The major radioactivity was metabolized by the hepatic system.A two-compartment model of C=4.49e^(-0.083t)+ 1.42e^(-0.0016t)was established,and the half life was 8.35 min in blood.In conclusion,the new radio-ligand ^(99)Tc^m-N-ethyl-N_2S_2-Memantine has a moderate affinity and specific binding to NMDA receptor,and can easily cross the blood-brain barrier(BBB).Therefore,it may be a potential NMDA receptor imaging agent.展开更多
The synthesis and biodistribution of β-amyloid plaques imaging agent [131I]-2- (4′-dimethylaminophenyl)- 6-iodoimidazo[1,2-α] pyridine ([131I]IMPY) were reported. The chemical structure of the labeling precursor 2...The synthesis and biodistribution of β-amyloid plaques imaging agent [131I]-2- (4′-dimethylaminophenyl)- 6-iodoimidazo[1,2-α] pyridine ([131I]IMPY) were reported. The chemical structure of the labeling precursor 2-(4′-dimethylaminophenyl)-6-(tributylstannyl)imidazo[1,2-α] pyridine and all its intermediates were verified by IR,HNMR and MS. The radioiodinated compound was prepared using iododestannylation reaction by hydrogen per-oxide. Final radiochemical purity was above 95% determined by TLC. The in vivo biodistribution of [131I]IMPY in normal mice showed excellent brain uptake and washout, indicating this thioflavin-T based small molecular probe has potential for in vivo imaging amyloid deposits.展开更多
In order to explore this type of <sup>99m</sup>Tc-GH and N<sub>2</sub>S<sub>2</sub> ligands exchange reaction as a common method for the preparation of <sup>99m</sup>Tc-...In order to explore this type of <sup>99m</sup>Tc-GH and N<sub>2</sub>S<sub>2</sub> ligands exchange reaction as a common method for the preparation of <sup>99m</sup>Tc-N<sub>2</sub>S<sub>2</sub> complexes, detailed kinetic study of ligand exchange reaction between <sup>99m</sup>Tc-GH and ECD was carried out. This paper presents preliminary results from the study at different ligand concentrations and pH values. The ligand exchange reaction is a second order reaction. Its rate constant being pH dependent were determined as: k<sub>pH2</sub>=1.11×104 l.mol<sup>-1</sup>. min<sup>-1</sup>, k<sub>pH5</sub>=1.34×10<sup>4</sup> l.mol<sup>-1</sup> min<sup>-1</sup>, kpH6=2.24×10<sup>4</sup> l. mol<sup>-1</sup>.min<sup>-1</sup>.展开更多
Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimer's disease(AD). The existence of neurofibrillary tangles(NFTs) consisting of tau p...Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimer's disease(AD). The existence of neurofibrillary tangles(NFTs) consisting of tau protein are one kind of the pathological features of AD, and its level of severity is correlated with the stage of AD.However, no clinically approved positron emission tomography(PET) probe is currently available for selective imaging of neurofibrillary tangles on patients. In this paper, we report our studies on biological characteristics of [18F]-THK523 as a novel tau imaging probe. With low molecular weight, [18F]-THK523 is stable, electrically neutral, lipophilic and non-mass concentration-dependent. Preliminary biological studies have shown the excellent properties of [18F]-THK523 as brain imaging tracer for further research.展开更多
文摘AIM: To investigate the effects of the WWOX gene on the human hepatic carcinoma cell line SMMC-7721. METHODS: Full-length WWOX cDNA was amplified from normal human liver tissues. Full-length cDNA was subcloned into pEGFP-N1, a eukaryotic expression vector. After introduction of the WWOX gene into cancer cells using liposomes, the WWOX protein level in the cells was detected through Western blotting. Cell growth rates were assessed by methyl thiazolyl tetrazolium (MTT) and colony formation assays. Cell cycle progression and cell apoptosis were measured by flow cytometry. The phosphorylated protein kinase B (AKT) and activated fragments of caspase-9 and caspase-3 were examined by Western blotting analysis. RESULTS: WWOX significantly inhibited cell proliferation, as evaluated by the MTT and colony formation assays. Cells transfected with WWOX showed significantly higher apoptosis ratios when compared with cells transfected with a mock plasmid, and overexpression of WWOX delayed cell cycle progression from G1 to S phase, as measured by flow cytometry. An increase in apoptosis was also indicated by a remarkable activation of caspase-9 and caspase-3 and a dephosphorylation of AKT (Thr308 and Ser473) measured with Western blotting analysis. CONCLUSION: Overexpression of WWOX induces apoptosis and inhibits proliferation of the human hepatic carcinoma cell line SMMC-7721.
基金supported by the Innovation Fund for Technology Based Firms (06C26213201075)National High Technology Research and Development Program of China (863 Program) (2008AA102415)
文摘A competitive indirect time-resolved fluoroimmunoassay(TRFIA) was developed for detection of zearalenone(ZEN) in cereals,in which ZEN conjugated to bovine serum albumin(BSA) is used as solid-phase antigen.A competitive indirect TRFIA was conducted by simultaneously incubating ZEN in standard or extracted samples with anti-ZEN monoclonal antibody over ZEN-BSA coated plates,and then determining the bound ZEN monoclonal antibody with goat anti-mouse europium conjugate.Samples were extracted with methanol/water...
基金Supported by the National Natural Science Foundation of China (No.20801024)Wu Jieping Medical Found(No.32067500615)
文摘A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in conditions of 0.1 mg SnCl2.2H2O at pH 6.0 and 99TcmO4? in aqueous solution for 20 min at room temperature. The labeling yield and radiochemical purity of 99Tcm-PIDP are both higher than 95%. The biodistribution results show that the bone uptake is up to 8.47% ID/g which is the maximum of bone uptake at 30 min after injection of 99Tcm-PIDP in mice. The pharmacokinetic parameters can be estimated from the exponential equation of C=59.565e-11.307t+2.069e-1.211t. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-PIDP. The results indicate that 99Tcm-PIDP has highly selective uptake in the skeletal and low uptake, rapid clearance in soft tissues, so it would be a potential novel bone imaging agent.
基金the Natural Science Foundation of Jiangsu Province(BK20181128)333 Project of Jiangsu Province(BRA2016518)Jiangsu Provincial Medical Youth Talent(QNRC2016626)。
文摘Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.
基金supported by grants from the National Natural Science Foundation of China(81471736,81671760 and 81873910)Scientific Research Transformation Special Fund of Heilongjiang Academy of Medical Sciences(2018415)Scientific Research Project of Health and Family Planning Commission of Heilongjiang Province(CR201807)
文摘Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value(SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer(CRC) in mice. Methods: Colorectal liver metastases(CRLM) xenograft models were established by injecting tumor cells(LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. ^(18)F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^(18)F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the ^(18)F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1 α(HIF-1 α) and serum starvation-induced glucose transporter 1(GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, ^(18)F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between ^(18)F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ^(18)F-FMISO SUVmax ratio and HIF-1 α or GLUT-1 expression in tumor-bearing tissues. Conclusions: ^(18)F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.
基金Supported by Jiangsu Province’s Key Medical Talents Program(No.RC2007097)Natural Science Foundation of Jiangsu Province,China(No.BK2010154)Science Foundation of Health Department of Jiangsu Province(No.H201226)
文摘Asialoglycoprotein receptor(ASGP-R)is a hepatic membrane receptor that uniquely exists on the surface of mammalian hepatocytes,and has been used as target of liver functional imaging agents for many years.We labeled the Galactosyl-neoglycoalbumin(NGA)with 18F to get a PET molecular probe 18F-FB-NGA and evaluated its ability as a liver functional PET imaging agent.The 18F-FB-NGA was prepared with NGA by conjugation with Nsuccinimidyl-4-18F-fluorobenzoate(18F-SFB)and purified with PD-10 desalting column.The radiolabeling yield and radiochemical purity of 18F-FB-NGA were determined by radio-HPLC.Starting with 18F-F–,the total time for 18F-FB-NGA was about 120±10 min.The decay-corrected radiochemical yield is about 25–30%.The radiochemical purity of purified 18F-FB-NGA was more than 98%.Labeled with 185–1850 MBq 18F-SFB,the specific activity of 18F-FBNGA was estimated to be 7.83–78.3 TBq/mmol.Biodistribution of 18F-FB-NGA in normal mice was investigated after injection through the tail vein.The results showed that the liver accumulated 39.47±3.42 and 12.12±6.11%ID/g at 10 and 30 min after injection,respectively.Dynamic MicroPET images in mice were acquired with and without block after injection of the radiotracer,respectively.High liver activity accumulation was observed at 5 min after injection in normal group.On the contrary,the liver accumulation was significantly lower after block,indicating the specific binding to ASGP-R.18F-FB-NGA is probably a potential PET liver imaging agent.
文摘99mTc-HMIBP, a new bone-imaging agent, was prepared by the reduction of 99mTc-pertechnetate in the presence of SnCl2?2H2O. The effects of the amounts of SnCl2?2H2O and HMIBP and the pH value on the labeling yield and radiochemical purity of 99mTc-HMIBP were investigated. When the amounts of SnCl2?2H2O and HMIBP were more than 10 μg and 2.5 mg, respectively, the pH value was between 2 and 7, and the labeling reaction contin- ued for 10 min, both labeling yield and radiochemical purity of 99mTc-HMIBP were more than 90%. The biodistribu- tion in rats and bone scan in rabbits were also studied. The results showed that the bone uptake is up to 7.94%ID/g at 30 min after injection of 99mTc-HMIBP, bone-to-muscle and bone-to-blood uptake ratios were 20.89 and 16.89, re- spectively. The clear bone image was obtained at 120 min after injection of 99mTc-HMIBP and clearance in soft tissue was visible. All of the above-mentioned results suggested that 99mTc-HMIBP may be a potential bone-imaging agent.
基金support from the National Natural Science Foundation of China(Grant No.:22076069)the Natural Science Foundation of Jiangsu Province(Grant No.:BK20201135)+1 种基金the Major Scientific Research Project of Jiangsu Commission of Health(Grant No.:ZDA2020007)the Science Technology and Development Project of Wuxi(Grant No.:Y20212013).
文摘Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,^(68)Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer ^(68)Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
基金This study was supported by grants from the National Key Re-search and Development Program of China(2019YFC0118100)the National Natural Science Foundation of China(81671760,81873910 and 82001860)+4 种基金Scientific Research Transformation Special Fund of Heilongjiang Academy of Medical Sciences(2018415)Scientific Research Project of Health and Family Planning Commission of Heilongjiang Province(201812 and 201622)Beijing Scholars Pro-gram([2015]160)Beijing Friendship Hospital Seed Project of Cap-ital Medical University(YYZZ201919)Beijing Postdoctoral Re-search Foundation(2020-Z2-022)。
文摘Background:Positron emission tomography (PET) imaging is a non-invasive method to visualize and quantify the tumor microenvironment.This study aimed to explore the feasibility of ^(18)F-AIF-NOTA-E[PEG_(4-c)(RGDfk)]_(2) (denoted as ^(18)F-RGD) PET quantitative parameters to distinguish the angiogenesis in colorectal cancer (CRC) mice which has different metastatic potential.Methods:Twenty Lo Vo and twenty LS174T of CRC liver metastases animal models were established by implantation of human CRC cell lines via intrasplenic injection.Radiotracer-based micro-PET imaging of animal model was performed and the uptake of ^(18)F-RGD tracer in the tumor tissues was quantified as tumor-to-liver maximum or mean standardized uptake value (SUVmax or SUVmean) ratio.Pearson correlation was used to analyze the relationship between radioactive parameters and tumor markers.Results:The SUVmax and SUVmean ratios of Lo Vo model were significantly higher than those of LS174T in both liver metastasis and primary tumor lesions (P<0.05).A significant difference was observed in both vascular endothelial growth factor (VEGF) and Ki67 expressions between Lo Vo and LS174T primary tumors (P<0.05).The tumor-to-liver SUVmax or SUVmean ratio of ^(18)F-RGD showed a moderate correlation with VEGF expression (r=0.5700,P=0.001 and r=0.6657,P<0.001,respectively),but the SUVmean ration showed a weak correlation with Ki67 expression (r=0.3706,P<0.05).The areas under the receiver operating characteristic (ROC) curves of ^(18)F-RGD SUVmean ratio,SUVmax ratio for differentiating Lo Vo from LS174T tumor were 0.801 and 0.759,respectively.Conclusions:The tumor-to-liver SUVmean ratio of ^(18)F-RGD was a promising image parameter for the process of monitoring tumor angiogenesis in CRC xenograft mice model.
基金Supported by National Natural Science Foundation,Nos.81171399,51473071,81101077,21401084,81401450 and 81472749Jiangsu Province Foundation,Nos.BE2014609,BE2012622,BL2012031 and BM2012066Wuxi Foundation,No.CSZ0N1320
文摘Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.
文摘Eu-chelate were used to construct a two-site sandwich-type assay for pepsinogen Ⅰ (PGI) with time-resolved fluoroimmunoassay (TRFIA) as a detection technique. On the noncompetitive assay, captured monoclonal antibodies (McAbs) coated on wells were directed against a specific antigenic site on the PGI. Another McAbs, called as labeling McAbs, were prepared with the Eu-chelate of N-(p-isothiocyanatobenzyl)-diethylenetriamine-N, N, N, N-tetraacetic acid and directed against a different antigenic site on the PGI. The fluorescence counts of bound Eu^3+ -McAbs were measured with the auto DELFIA1235 system. The PGI in sera from healthy volunteers were determined by PGI-TRFIA. The within-run and between-run CVs of the PGI-TRFIA were 1.9% and 4.7%, respectively, and the recovery rate was 102.65%. The assay had a detection limit of 0.05 μg· L^-1. The PGI-TRFIA provided a linear response from 3.5 to 328 μg· L^-1. The cross-reacting rate with pepsinogen Ⅱ was negligible. The linear correlation of PGI-TRFIA and radioimmunassay measurements resulted in a correlation coefficient of 0.977. The means of healthy volunteers were 154 ±43 μg·L^-1 for serum PGI. The availability of a highly sensitive, reliable, and convenient method for quantifying PGI will allow investigations into the possible diagnostic value of this analyte in various clinical conditions, including gastric carcinoma, duodenal ulcer, gastritis and severe atrophic gastritis.
基金Supported by National Natural Science Foundation of China (20573048 and 20676051)Natural Science Foundation of Jiangsu Province (BK2008111, BK2008112)Department of Health of Jiangsu Province (H200624)
文摘Technetium-99m-labeled-5-{2-sulfanylethyl-[2-(2-sulfanylethylamino)acetyl]amino}-methyl-2′-deoxy- uridine (99mTc-ANMdU) was reported. The precursor ANMdU was synthesized by six-step reactions and all intermediates were verified with MS and 1HNMR. Using SnCl2 as reducing agent, a labeling reaction was carried out at 100°C for 30 min. The radiochemical purity of the 99mTc-ANMdU was 96.68%. Partition coefficients were 0.92 and 0.70 at pH 7.0 and 7.4 of the phosphate buffer saline, respectively. Biodistribution of 99mTc-ANMdU in normal mice showed that the initial uptake of 99mTc-ANMdU in vivo and the clearance was rapid.
文摘TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99TcmO4 with SnCl2·2H2O in aqueous solution for 10 min at room temperature. Both labeling yield and radiochemical - purity of Tcm-TADP were more than 95%. The biodistribution in rats and bone scan in rabbits were also studied. The 99 uptake of organ was expressed as %ID/g. The results showed that the bone uptake is up to 17.17%ID/g which is the maximum of bone uptake at 30 min after injection of Tcm-TADP in rats, bone-to-muscle and bone-to-blood uptake 99 ratios were 61.32 and 13.21, respectively. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-TADP and clearance in soft tissue was visible. The preparation of 99Tcm-TADP was convenient and 99Tcm-TADP exhibited high uptake in bone, and it would be a potential new bone imaging agent.
基金Supported by National Natural Science Foundation of China (No.81202032)Key University Science Research Project of Jiangsu Province (No. 16KJB320004)+2 种基金Jiangsu Provincial Health and Family Planning Commission Foundation (No.Z201502)Jiangsu Provincial Health and Family Planning Research Projects (No.H2018029)Key Laboratory of Nuclear Medicine of the Ministry of Health, Jiangsu Provincial Key Laboratory of Molecular Nuclear Medicine (No.KF201501)
文摘The interleukin-11(IL-11)and the IL-11 receptorα-subunit(IL-11Rα)have been demonstrated to regulate the invasion and proliferation of tumor cells.Our study intends to evaluate a noninvasive imaging of IL-11Rαexpression in breast tumors using near-infrared(NIR)fluorescent dye Cy7-labeled IL-11 mimic peptide CGRRAGGSC.This work evaluated the IL-11Rαexpression of breast tumor cells and the binding status of this peptide to IL-11Rαin vitro and in vivo by using Western blotting,immunofluorescence staining and near-infrared fluorescence imaging.Our biochemical study showed that IL-11Rαwas overexpressed in breast tumor cells(MCF-7).The cell-binding assay demonstrated specific binding of peptide CGRRAGGSC to MCF-7 cells in vitro.In vivo imaging results showed that NIR fluorescent signals of Cy7-CGRRAGGSC were selectively accumulated in tumor and metabolic organs.While in the blocking experiment,free CGRRAGGSC obviously blocked the concentration of the Cy7-CGRRAGGSC in the tumors.These results suggested that IL-11Rαmay be used as a potential target for noninvasive imaging in IL-11Rαoverexpressed tumors.Furthermore,the imaging agent of near-infrared fluorescent dye Cy7-labeled CGRRAGGSC is suitable for IL-11Rαexpression imaging study in vivo.
基金Supported by National Natural Science Foundation of China(No.30770602)Natural Science Foundation of Jiangsu Province,China(Nos.BK2010157 and BK2011167)
文摘The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stannous fluoride (SnF 2 ) as reducing agent. Biological characteristics of 99m Tc-PQQE include lipophilic and the charge properties were compared to 99m Tc-PQQ. The biodistributions of 99m Tc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99m Tc-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2β) results indicate that the residence time of 99m Tc-PQQE (203.92) in the body is twice as long as 99m Tc-PQQ (100.45). The uptake of 99m Tc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99m Tc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99m Tc-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that 99m Tc-PQQE has some specific targeting to the NMDA receptor.
基金Supported by the Society Development Fund of Jiangsu Province (No.BS94012)
文摘To evaluate the clinical value of combined determination of serum PGⅠ, PGⅡ and GAS for early diag-nosis of gastric cancer, the serum levels of PGⅠ, PGⅡ and GAS in 190 healthy controls and 129 patients with gas-tric disorders were measured by RIA. The 129 patients include 68 cases of gastric cancer. The results showed that the serum levels of PGⅠ and PGⅠ/PGⅡ ratio in gastric cancer patients were obviously lower than those in healthy controls, while comparing with controls, the serum GAS levels were significantly higher. The diagnostic accuracy of the determinations for gastric cancer was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) levels of serum PGⅠ, PGⅠ/PGⅡ ratio and GAS were 0.833, 0.842 and 0.851, respec-tively. As serum PGⅠ or PGⅠ/PGⅡ ratio or GAS were combined, the sensitivity and specificity of determination for gastric cancer diagnosis were 94.2% and 73.4%, respectively. All these results indicated that the combined deter-mination of serum PGⅠ, PGⅡ and GAS levels may be used as a tool for primary screening of gastric cancer.
基金Supported by National Natural Science Foundation(No30770602)Jiangsu Natural Science Foundation(No BK2008111)
文摘The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-memantine.The affinity and specificity were determined by radio-ligand receptor binding assay(RRA).Biodistribution in vivo in mice was performed.The results showed that ^(99)Tc^m-N-ethyl-N_2S_2-memantine bound to a single site on NMDA receptor with a K_d of 584.32 nmol/L and a B_(max)of 267.05 nmol/mg.A competitive analysis showed that such specific binding could be inhibited by specific inhibitors of NMDA receptor,such as ketamine and(+)-MK-801.The biodistribution exhibited rapid uptake and favorable retention in mice brains.The major radioactivity was metabolized by the hepatic system.A two-compartment model of C=4.49e^(-0.083t)+ 1.42e^(-0.0016t)was established,and the half life was 8.35 min in blood.In conclusion,the new radio-ligand ^(99)Tc^m-N-ethyl-N_2S_2-Memantine has a moderate affinity and specific binding to NMDA receptor,and can easily cross the blood-brain barrier(BBB).Therefore,it may be a potential NMDA receptor imaging agent.
基金Jointly supported by a grant from National Natural Science Foundation (30470496), a grant from "135" Medicinal Momentous Pro-ject of Jiangsu Province (RC2002068), a grant from Department of Personnel of Jiangsu Province and a grant from Natural Science Foundation of Jiangsu Province (BK2004423).
文摘The synthesis and biodistribution of β-amyloid plaques imaging agent [131I]-2- (4′-dimethylaminophenyl)- 6-iodoimidazo[1,2-α] pyridine ([131I]IMPY) were reported. The chemical structure of the labeling precursor 2-(4′-dimethylaminophenyl)-6-(tributylstannyl)imidazo[1,2-α] pyridine and all its intermediates were verified by IR,HNMR and MS. The radioiodinated compound was prepared using iododestannylation reaction by hydrogen per-oxide. Final radiochemical purity was above 95% determined by TLC. The in vivo biodistribution of [131I]IMPY in normal mice showed excellent brain uptake and washout, indicating this thioflavin-T based small molecular probe has potential for in vivo imaging amyloid deposits.
文摘In order to explore this type of <sup>99m</sup>Tc-GH and N<sub>2</sub>S<sub>2</sub> ligands exchange reaction as a common method for the preparation of <sup>99m</sup>Tc-N<sub>2</sub>S<sub>2</sub> complexes, detailed kinetic study of ligand exchange reaction between <sup>99m</sup>Tc-GH and ECD was carried out. This paper presents preliminary results from the study at different ligand concentrations and pH values. The ligand exchange reaction is a second order reaction. Its rate constant being pH dependent were determined as: k<sub>pH2</sub>=1.11×104 l.mol<sup>-1</sup>. min<sup>-1</sup>, k<sub>pH5</sub>=1.34×10<sup>4</sup> l.mol<sup>-1</sup> min<sup>-1</sup>, kpH6=2.24×10<sup>4</sup> l. mol<sup>-1</sup>.min<sup>-1</sup>.
基金Supported by National Natural Science Foundation of China(Nos.81271516 and 81371625)Program of Shanghai Science and Technology Commission(Nos.13JC1401503 and 14DZ1930402)+1 种基金Shanghai Municipal Health and Family Planning Commission(No.2013313)Exchange Programme Foundation of Doctoral Student under the Office for Graduate Medical Education,Fudan University
文摘Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimer's disease(AD). The existence of neurofibrillary tangles(NFTs) consisting of tau protein are one kind of the pathological features of AD, and its level of severity is correlated with the stage of AD.However, no clinically approved positron emission tomography(PET) probe is currently available for selective imaging of neurofibrillary tangles on patients. In this paper, we report our studies on biological characteristics of [18F]-THK523 as a novel tau imaging probe. With low molecular weight, [18F]-THK523 is stable, electrically neutral, lipophilic and non-mass concentration-dependent. Preliminary biological studies have shown the excellent properties of [18F]-THK523 as brain imaging tracer for further research.