Objective To fabricate an ultrasound/fluorescence bi-modal contrast agent by encapsulating fluorescent quantum dots into polymeric ultrasound contrast agent microbubbles.Methods Polylactic acid (PLA,500 mg),(1R)-(+)-camphor (50 mg) and CdSe/ZnS quantum dots (0.5 ml,2.3 μmol/L)were dissolved or dispersed in dichloromethane (10 ml) to form in an organic phase.Ammonium carbonate solution and poly (vinyl alcohol) solution were employed as the internal and external water phase,respectively.The fluorescent microbubbles were generated using double emulsion solvent evaporation and lyophilization methods.The morphology and illumination were characterized by scanning electron microscopy (SEM) and fluorescence spectrophotometry.Synchronized contrast-enhanced ultrasound and fluorescence imaging was acquired by injecting fluorescent microbubbles into the silicone tube coupled to a self-made ultrasound/fluorescence imaging device.Ultrasound/fluorescence bi-modal in vivo imaging was acquired on the kidney of New Zealand rabbits and suckling mice.Results The fluorescent microbubbles were hollow spheres with an averaged diameter of (1.62 ± 1.47) μm.More than 99％ of these microbubbles were less than 8 μm in diameter,which meeted the size criteria for ultrasound contrast agents.The fluorescence emission peak of the microbubbles appeared at 632 nm,indicating that good luminescence properties of quantum dots were maintained.In vitro ultrasound/fluorescence imaging showed no echoic signal when the silicone tube was filled with saline,but there was a strong echo when filled with fluorescent microbubbles.The liquid column with fluorescent microbubbles emitted red luminescence under ultraviolet irradiation.The kidney of the rabbit was remarkably enhanced after the administration of fluorescent microbubbles.Bright fluorescence could be observed at the injection site of the suckling mice via subcutaneous injection.Conclusions A bi-modal but single contrast agent based on polymeric microbubbles has been successfully fabricated for the use of ultrasound and fluorescence imaging.It retains the good characteristics of both echogenicity and fluorescence,which complement each other in case of limitations imposed by uni-modal,single agents.

Objective To assess the diagnostic accuracy of NT-proBNP in hypertension patients by observing the effect of decreased GFR on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with different cardiac function.Methods Eighty-nine hypertension patients were divided into two groups based on the results of UCG.Forty-three patients had normal left ventricular function and 46 patients had dysfunction.GFR,NT-proBNP and other biochemical markers of cardiac and renal function were measured.The factors affecting the NT-proBNP concentration under normal left ventricular function were analyzed,and the diagnostic value of NT-proBNP affected by normal or decreased GFR(＞ 80 ml/min or ≤80 ml/min) under different left ventricular functions were further assessed.The two-sample t test,rank sum test and multiple regression analysis were used to analyze their statistical difference and relationship.Results In patients with normal left ventricular function,GFR (β =-0.361,P ＜ 0.05) and left ventricular end-diastolic diameter (LVEDD,β =0.385,P ＜ 0.05) were significant factors to NT-proBNP level.They were both meaningful compared with LVEF (β =0.189,P ＞0.05) and septal thickness (β =0.003,P ＞ 0.05).The median concentration of NT-proBNP was 13.18 and 24.14 μg/L in patients with normal left ventricular function and dysfunction,respectively (Z =-3.19,P ＜ 0.01).While in patients with decreased GFR,6 cases with normal left ventricular function and 19 cases with dysfunction had a median concentration of NT-proBNP of 38.45 and 44.20 μg/L,respectively (Z =-0.45,P ＞ 0.05).In patients with normal GFR,37 cases with normal left ventricular function and 27 cases with dysfunction had a median concentration of NT-proBNP of 12.51 and 20.31 μg/L,which was lower than that of patients with decreased GFR (Z =-2.76,both P ＜ 0.05).The NT-proBNP concentration had no significant difference between patients of normal left ventricular function with decreased GFR and patients of dysfunction with normal GFR (38.45 and20.31 μg/L,Z=-2.18,P＞0.05).Conclusion In hypertension patients,the effect of decreased GFR on assessing the diagnostic accuracy of NT-proBNP for left ventricular dysfunction should be considered.

Objective To investigate the clinical value and the expression of OX40/OX40L from lymphocytes of patients with Graves' disease (GD) before and after 131I therapy.Methods The expression of OX40/OX40L on T,B lymphocytes and the percentage of lymphocyte subsets were analyzed using immunofluorescence staining and flow cytometry in 32 patients with GD before and after 131I therapy.Twenty-five healthy subjects were considered as the control group.The data between GD patients and controls were compared with two-sample t test.The correlation between the expression of OX40/OX40L and the function of thyroid (FT3,FT4 and TRAb level) was performed with linear correlation analysis.Results Compared with the healthy subjects,the percentage of CD4+ T cells and ratio of CD4+/CD8+ were decreased ((34.36 ±6.73)％ vs (45.60-±5.72)％,t=2.634; 1.24±0.26 vs 1.84±0.37,t=2.125,both P＜0.05).Whereas the percentage of CD19+ B cells in patients with GD were significantly higher than that in healthy subjects ((21.42 ±3.92)％ vs (15.35 ± 3.15)％,t =2.653,P ＜0.05).The expression of OX40 increased in CD4+ T lymphocytes ((12.92 ± 2.26) ％) and OX40L expression was up-regulated in CD19+ B lymphocytes ((15.33 ± 3.75)％) of patients with GD,compared with the healthy subjects ((4.19 ±1.45) ％ and (8.64 ± 1.73) ％,respectively,t =2.112 and 2.467,both P ＜ 0.05).The expression of OX40 in CD4+ T lymphocytes ((7.65 ± 1.64) ％) and OX40L in CD19+ B lymphocytes ((11.50 ±2.72)％) were increased after 131I therapy(t =2.795,2.393,both P ＜0.05).The thyroid functions of 32 GD patients were improved.The levels of FT3,FT4 and TRAb decreased significantly after 131I treatment (from 20.79 ±6.05 to 4.53 ± 2.54,from 49.65 ± 10.12 to 13.69 ± 4.35,and from 24.78 ± 8.46 to 11.74 ±6.19,respectively; t =2.219,2.441 and 2.293,all P＜0.05).The levels of FT3 and FT4 were positively correlated with the percentage of OX40 expression in CD4+ T lymphocytes (r =0.65 and 0.73,both P ＜ 0.05).TRAb was positively correlated with CD19+ OX40L + B lymphocytes (r =0.76,P ＜ 0.05).Conclusions OX40/OX40L may play an important role in the activation of lymphocytes,the production of antibodies,and participate in the pathogenesis and progression of GD.131I therapy not only damages most of the thyroid follicular epithelial cells by its β ray,but also facilitates GD improvement by regulating T and B lymphocyte functions.

Objective To explore the clinical application and safety of treatment of percutaneous radioactive 125I seed implantation treatment in lung metastases under CT guidance.Methods Twenty-seven lung metastatic malignancy cases (67 nodules) were studied.Eighteen cases (46 nodules) were hepatic cancer,4 cases (9 nodules) were prostate cancer,and 5 cases (12 nodules) were breast carcinoma.Diameters of lung nodules ranged from 0.5 cm to 4.0 cm with an average diameter of 2.1 cm.125I seeds were embedded under CT guidance,using 2 to 33 particles/nodule with an activity of 18.5 to 29.6 MBq/grain for each particle.Tumor matched peripheral dose was 90-120 Gy.Postoperative validation and quality evaluation followed.Results Four months later,24 nodules showed CR,30 showed PR,5 showed NC and 8 showed PD.The total effective rate was 80.6％ (54/67).In the course of treatment,11 patients had pneumothorax,3 had heavy lung compression and 4 had hemoptysis.All conditions were improved by pleural puncture or under close follow-up observation.Conclusion 125I seed implantation is an effective and safe technique in treatment of metastatic lung tumors under CT guidance.

Objective To investigate the clinical efficacy of 90Sr-90Y applicator combined with propranolol (inderal) treatment for infants with large areas of cutaneous hemangiomas.Methods Thirty-nine infants with large areas of cutaneous hemangiomas were randomly divided into two groups:study group (n =18) treated with 90Sr-90Y applicator in conjunction with propranolol,and control group (n =21) treated by 90Sr-90Y applicator only.The results of curative effects between the two groups were analyzed using rank sum test and x2 test.Results The cure rate,remission rate and effective rate for the study group were 44.4％(8/18),55.6 ％ (10/18) and 100.0％ (18/18),respectively,and the corresponding rates for the control group were 14.3％ (3/21),52.4％ (11/21) and 66.7％ (14/21),respectively.The effective rate in the study group was significantly higher than that in the control group (Z =-2.861,P ＜ 0.05).The adverse reaction rates in the study and control groups were 66.7％ (12/18) and 19.0％ (4/21 ;x2 =9.084,P ＜0.05),respectively.Conclusion Combined propranolol with 90Sr-90Y treatment for large infantile hemangiomas is clinically effective,but its side effects should be closely monitored.

Objective To investigate changes of striatal DAT following hypoxic ischemic (HI)brain injury in newborn piglets using 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (CFT) PET/CT,and to evaluate the value of 11C-CFT PET/CT in brain injury.Methods Newborn piglets with HI brain injury (n =20) were taken as a model group,and five piglets were used as a control group.Radioligand 11CCFT (55.5-74.0 MBq) was injected through the jugular vein,and PET/CT imaging was performed to observe the changes of striatal DAT in newborn piglets.The ST/occipital lobe (OC) ratio was calculated.Model group was divided into 0-6 h,20-24 h,44-48 h and 68-72 h sub-groups after HI in accordance with the imaging time.The piglets were sacrificed immediately after 11C-CFT PET/CT scanning,and then the brains were removed for pathological analysis.Data analysis was performed with one-way analysis of variance and Pearson linear correlation analysis.Results After intravenous injection of 11C-CFT,the radioactivity accumulation in cortical,striatum,and cerebellum was shown clearly in the control and model groups.The radioactivity accumulation was lower in the white matter.The radioactivity in cortical and cerebellum exhibited decreased with time,while the striatum was still clear.After HI,the ST/OC activity ratio in the striatum was initially increased,and the ratio of 0-6 h group (1.34 ± 0.04) was statistically significant compared with that of thecontrol group (1.18 ± 0.06 ; F =4.658,P ＜ 0.05),followed by a gradual decrease.ST/OC ratios of other HI subgroups were 1.27 ±0.01,1.27 ±0.10 and 1.18 ±0.05,respectively.There was a positive correlation between the number of DAT positive neurons ((13 ± 3),(13 ± 4),(8 ±3) and (4 ±4)/high power field) and 11C-CFT ST/OC activity ratios (r =0.844,P ＜0.05).Conclusion 11C-CFT PET/CT study can accurately reflect the changes of DAT in the striatum,and the amount of DAT is related to the severity of the ischemic insult in a newborn piglet model of HI.

Objective To evaluate if 18F-FLT PET imaging could be used as a new clinical method to predict tumor radiosensitivity.Methods MDA-MB-231 and LN229 cells were irradiated with doses of 0,8 and 16 Gy of 6 MV photon energy,then soft agar assay and cellular uptake of 18F-FLT were performed on the 2 cell lines.The t test and one-way analysis of variance were used for the two groups and data before and after irradiation.The MDA-MB-231 and LN229 tumor xenografts were prepared by injecting the tumor cells into the right limbs of female BALB/c nu/nu mice.Once tumors reached a diameter of 10 mm,the two types of mice were divided randomly into 3 groups (20 mice per group) according to the irradiation doses (0,8 and 16 Gy).After irradiation,18F-FLT PET imaging and immunohistochemical staining were conducted.Then correlations between 18F-FLT SUVtumor/SUVmuscle ratio (T/M ratio) and TK1 labeling index percentages (LITK1) were tested using linear correlation analysis.Results The survival fraction of MDA-MB-231 and LN229 cells after irradiated with 8 Gy were (59.73 ± 4.3) ％ and (93.41 ± 3.75) ％,respectively (t =-13.20,P ＜ 0.001).When the dose increased to 16 Gy,the survival fraction decreased to (43.57 ±4.06) ％ and (81.77 ± 4.42) ％,respectively(t =-14.24,P ＜ 0.001).In MDA-MB-231 cells,the cellular uptake of 18F-FLT after irradiation with 8 Gy declined rapidly to (18.32 ± 1.38) kBq/105 cells ((128.22 ± 8.24) kBq/105 cells with the dose of 0 Gy,F =266.41,P ＜ 0.01),and maintained this low level till 72 h.For the LN229 cells,the cellular uptake decreased to (9.87 ± 1.30) kBq/105 cells after 8 Gy irradiation ((134.88 ± 6.59) kBq/105 cells with the dose of 0 Gy,F =346.06,P ＜ 0.01),then increased gradually to (127.17 ± 9.08) kBq/105 cells at 72 h (F =346.06,P ＞ 0.05).The dynamic changes of 18F-FLT cellular uptake in the two cells had the same pattern after being treated with 16 Gy irradiation.In the 18F-FLT PET image of MDA-MB-231 tumor mice after 8 Gy radiotherapy,the T/M ratio decreased to 0.78 ± 0.39 at the first day,but it was 2.84 ± 0.29 before radiotherapy (F =39.78,P ＜0.01).Then the ratio increased slowly,and it was still lower than the baseline at 7 d after radiation (F =39.78,P ＜0.01).The same pattern could be seen in the group of 16 Gy irradiation.In LN229 tumor mice treatment with 8 Gy irradiation,the T/M ratio increased to 2.41 ±0.47 at the first day,and it was 1.58 ±0.29 before radiotherapy (F =34.01,P ＜ 0.05).The ratio decreased steadily to 0.66 ± 0.32 (F =34.01,P＜0.05) at 7 d after radiotherapy.However,in the treatment group with 16 Gy,the T/M ratio decreased gradually and reached 0.44 ± 0.22 at 7 d (F =41.85,P ＜ 0.01).A correlation was found between 18F-FLT T/M ratio and LITK1 (8 Gy:r=0.67,0.73; 16 Gy:r=0.73,0.69; all P＜0.01) in both tumor models.Conclusion 18F-FLT PET imaging may be used as a new assay to predict tumor radiosensitivity,but further investigation is needed before clinical application.

In both type 1 and type 2 diabetes mellitus,β-cell mass (BCM) is lost.Various treatments are developed to restore or reconstruct BCM.The development of non-invasive methods to quantify BCM in vivo offers the potential for early detection of β-cell dysfunction prior to the clinical onset of diabetes.PET imaging with radioligands that directly target the pancreatic β-cells appears promising.The ability to determine the BCM has been investigated in several targets and their corresponding radiotracers,including radiolabeled receptor ligands,antibodies,metabolites and reporter genes.Therefore,we summarize the recent progress in radionuclide molecular imaging of pancreatic β-cells.

Objective To study whether Bay 11-7082,a nuclear factor-kappa B (NF-KB) inhibitor,could enhance the treatment efficacy of 131I on DTC in nude mice.Methods Total thyroid ablation nude mice models were prepared by intraperitoneal injection of 37 MBq 131I.The xenografted mice were divided into4 groups (18/group):131I group,Bay 11-7082 group,combination of 131I and Bay 11-7082 group and control group.Drug dosages were given as:intraperitoneal injection of 37 MBqT31I on day 1 in the 7th week in the 131I group; intraperitoneal injection of 10 mg/kg Bay 11-7082 on day 1,2 and 3 in the 7th week in the Bay 11-7082 group; intraperitoneal injection of both 131I and Bay 11-7082 as above-mentioned in the combined treatment group; injection of saline in the control group.The xenografted tumor volume curves were drawn every 7 days.Pertechnetate imaging was performed before thyroid ablation.Post-ablative and post-therapeutic 131I whole body imaging was conducted.On day 7 in the 7th week,6 mice in each group were sacrificed and apoptotic staining was performed on excised xenograft tumors.Apoptosis index was determined as positive cells over total ceils × 100％.One-way analysis of variance and q test were performed for statistical analysis.Results Thyroid and stomach could be visualized on pertechnetate imaging before thyroid ablation.Post-ablative 131I imaging showed increased uptake by the thyroid gland.Post-therapeutic 131I imaging showed increased uptake by the malignant tumor lesions in both the 131I and combined groups.Tumor volume curves showed significant differences in volume changes among different methods of therapy from the end of the 8th week (F =11.91-246.56,all P ＜ 0.01).Combined treatment was more effective than single-therapies (q =3.36-14.99,all P ＜ 0.01).Apoptosis indices for the control group,131I group,Bay 11-7082 group and combined group were (0.28 ±0.15)％,(5.49 ±0.69)％,(6.82 ±0.72)％ and (16.21 ± 1.57) ％,respectively (F =304.40,P ＜ 0.01).Apoptosis index in the combined group was significantly higher than those in each single therapy group (q =15.33 and 13.33,both P ＜ 0.01).Conclusion NF-κB inhibition by Bay 11-7082 could effectively enhance the treatment efficacy of 131I on DTC.

Objective To investigate the usefulness of 13N-NH3 PET in detecting brain lesions which show hypometabolism on 18F-FDG PET.Methods 13N-NH3 PET imaging was performed for a prospective study in 18 patients with brain lesions that showed hypometabolism compared with normal brain tissue on 18F-FDG PET scans.Fourteen patients underwent 18 F-FDG PET imaging for initial diagnosis and 4 patients for detection of astrocytoma recurrence (13 males,5 females,age 20-68 (42.4 ± 12.6) years).Ten gliomas,1 metastatic tumor,1 dysembryoplastic neuroepithelial tumor (DNT) and 6 non-neoplastic lesions (including 3 cases of radiation necrosis,2 cases of encephalitic foci,and 1 case of ischemic lesion)were verified by histopathological examination (n =13) or clinical follow-up (n =5).The tumor-to-contralateral brain tissue ratios (T/C) were calculated by the ROI method.The diagnostic efficacy of 13N-NH3 PET was evaluated.Paired t test and two-sample t test were performed to analyze the differences of T/C between different groups.Results Seven (5 astrocytomas and 2 glioblastomas) of 12 brain tumors (sensitivity:58％,7/12) showed increased 13N-NH3 uptake (higher uptake than the contralateral brain tissue),while 3 low-grade gliomas,1 metastatic tumor,and 1 DNT showed decreased 13N-NH3 uptake (no uptake or lower uptake than the contralateral brain tissue).The uptake ratio of 13N-NH3 was significantly higher than that of 18 F-FDG (1.24 ± 0.66 vs 0.67 ± 0.24,t =-3.740,P ＜ 0.05) in the tumors.All six non-neoplastic lesions showed decreased 13N-NH3 uptake (specificity:6/6).The T/C ratios of 18F-FDG and 13N-NH3 in the non-neoplastic lesions were 0.68 ±0.15 and 0.70 ±0.19,respectively,and there was no significant difference between them (t =-0.246,P ＞ 0.05).The T/C ratio of 13N-NH3 in the tumors was significantly higher than that in the non-neoplastic lesions (1.24 ± 0.53 vs 0.70 ± 0.19,t =2.624,P ＜ 0.05).Conclusion 13N-NH3 PET imaging may be helpful to detect and differentiate brain tumors with hypometabolism as detected by 18 F-FDG PET imaging from non-neoplastic lesions with high specificity,especially for cerebral astrocytomas,but the sensitivity is relatively limited.