Study of 68Ga-NODAGA-RGD PET/CT in predicting short-term efficacy of tyrosine kinase inhibitor in the treatment of distant metastatic differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the clinical application of 68Ga-cyclo( L-arginylglycyl- L-α-aspartyl- D-tyrosyl-N6-(((4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)acetyl))- L-lysyl) (NODAGA-RGD) PET/CT to evaluate short-term efficacy of tyrosine kinase inhibitor (TKI) in distant metastatic differentiated thyroid cancer (dmDTC). Methods:From October 2019 to March 2023, 13 dmDTC patients (5 males, 8 females; age: 68(65, 69) years) from Nanjing First Hospital were retrospectively enrolled, of which 9 were clinically confirmed as radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and 4 were dmDTC without radioactive iodine treatment. All patients underwent 68Ga-NODAGA-RGD PET/CT to assess neovascularization of the target lesions (TL), and the SUV max and target background ratio (T/B) were recorded. After 3 months of TKI treatment (anrotinib ( n=9) or apatinib ( n=4)), change rates of the maximum diameter of TL and thyroglobulin (Tg) were measured. The correlation of SUV max, T/B and the change rate of the maximum diameter of TL were analyzed by Spearman rank correlation analysis. ROC curve analysis was performed for the effectiveness of the T/B and TKI therapy, and the difference of the remission rate of lesions was analyzed by Fisher exact test. Results:In 13 patients, 36 TL were measured by 68Ga-NODAGA-RGD PET/CT with SUV max of 5.44(3.43, 7.56) and T/B of 5.25(4.50, 7.23). The change rate of the maximum diameter of TL was -30%(-39%, -21%) and the change rate of Tg was -68%(-96%, -52%). T/B was negatively correlated with the change rate of the maximum diameter of TL after TKI therapy ( rs=-0.46, P=0.005), while SUV max was not correlated with the change rate of the maximum diameter of TL ( rs=0.03, P=0.883). ROC curve analysis showed that the optimal cut-off value for T/B was 4.95, with the AUC of 0.698, the sensitivity of 87.5%, and the specificity of 60.0%. Compared to lesions with T/B<4.95, those with T/B≥4.95 showed higher remission rate (2/14 vs 63.6%(14/22); P=0.006). After 3 months of TKI treatment, the disease control rate was 12/13. Conclusion:68Ga-NODAGA-RGD PET/CT can effectively reflect tumor neovascularization, predict efficacy of TKI therapy, and provide powerful imaging evidence for TKI therapy in dmDTC.

Characteristics of 18 F-Alfatide II PET/CT imaging in normal breast and malignant breast cancer / 中华核医学与分子影像杂志

Objective To investigate the characteristics of 18F-Alfatide II PET/CT imaging in normal breasts and breast cancer lesions.Methods From March 2016 to August 2017,22 female patients(age:(52±10)years)with suspected breast malignant nodules or masses were prospectively enrolled.All patients underwent 18F-Alfatide II PET/CT imaging prior to biopsy or surgery.The imaging characteristics of normal breasts were assessed visually and the difference of maximum standardized uptake value(SUVmax)in normal breasts and uterus between patients with and without menopause was compared,SUVmax of cancer lesions and normal breasts was also compared.Breast cancer lesions were classified according to the distribution characteristics of radioactive uptake,and molecular subtypes ware determined by immunohistochemistry and fluorescence in situ hybridization.The SUVmax of different morphological and molecular subtypes were analyzed.Two-sample t test and Pearson or Spearman correlation analysis were used to analyze the data.Results There were 23 breast cancer lesions(one patient had bilateral breast cancer lesions and one had a history of one-side breast resection),20 normal breasts and 21 normal uteruses.Those normal breasts and uteruses didn't show any malignant change after being followed up for more than 1 year(one patient had uterine fibroids resection).There was a slight increase of radioactivity uptake in the cord-like connective tissue region at the margin of the gland in 11 mammary glands,and the SUVmax was higher than that of glandular tissue in the central region(1_81±0.67 vs 0.79±0.37;t = 6.771,P<0.00l).Of the 11 cases,except for one patient whose uterus was removed,the other 10 patients were accompanied by increased diffuse radioactivity of the uterus.SUVmax of 19 normal breast connective tissues(1.31±0.80)and uterus(3.80+1.79)were positively correlated(r = 0.785,P<0.05).For patients with/without menopause(n= 11 each group),the SUVmax of normal breast connective tissues(0.72±0.39 vs 1.81±0.67)and uterus(2.04±0.39 vs 5.11 + 1.06)were significantly different(t values:4.42 and 8.66,both P<0.01).Different levels of radioactive uptake were observed in all 23 breast cancer lesions,with SUVmax of 6.93±3.97,which was significantly higher than the nipple,connective tissue and glandular tissue of normal breasts(t values:6.784-7.559,all P<0.05).According to the characteristics of the radioactivity uptake distribution of the lesion,among the 23 breast cancer lesions,5 were mass type,3 were nodular type,4 were diffuse type,and 11 were multi-focal/multi-center type,and the SUVmax of multi-focal/multi-center type was the highest(F=3.55,P<0.05).The SUVmax of basal-like breast cancer lesions(2.49±1.67)was lower than the other three molecular subtypes.Lesions with high level human epidermal growth factor receptor 2(HER2)positive expression had higher SUVmax.Conclusions 18F-Alfatide II PET/CT imaging shows that normal breasts have a slight radioactive distribution,mainly concentrate in the nipple and connective tissues around the glandular,and the uptake have a positive correlation with the radioactive uptake of the uterus.The degree of radioactive uptake of breast cancer lesions is significantly higher than that of normal breasts.Breast cancer lesions with different moqjhological features all have obvious radioactive uptake,especially the multi-focal/multi-center type.Different molecular subtypes have different radioactive uptake levels.SUVmax is lower in basal-like breast cancer lesions,and higher in HER2 positive expression lesions.

Diagnostic value of a novel RGD-peptide based tracer 18F-Alfatide II for breast cancer / 中华核医学与分子影像杂志

Objective To investigate the biodistribution of 18F-Alfatide II in patients with breast diseases and to compare its uptake with 18F-fluorodeoxyglucose(FDG)uptake.Methods A total of 44 female patients(age:(50.7±8.0)years)with clinically suspected breast cancer from December 2015 to May 2017 were prospectively enrolled and underwent 18 F-Alfatide II and 18F-FDG PET/CT prior to treatment.By drawing regions of interest in normal organs and breast lesions,differences between 18F-Alfatide II uptake and l8F-FDG uptake were evaluated in all patients.Paired t test,two-sample t test and Wilcoxon rank sum test were used for data analysis.Results There were 53 breast lesions confirmed by histopathology in 44 patients.Among them,42 lesions were malignant and the others were benign.The uptake of 18F-Alfatide II was very low in the brain,vocal cords,lungs,blood pool and muscle.But the renal cortex and bladder had high 18F-Alfatide II accumulation.Different levels of 18F-Alfatide II uptake were found in other normal organs including normal breast tissue.There were differences(t values:2.04-41.65,all P<0.05)between 18F-Alfatide II and 18F-FDG maximum standardized uptake value(SUVmax)and mean standardized uptake value(SUVmean)in many normal organs except for the choroid plexus,salivary glands,liver,colon and normal breast tissue.The uptake of 18F-Alfatide II was significantly lower than 18F-FDG in breast cancer lesions(SUVmax:3.77±1.78 vs 7.37±4.48,SUVmean:2.25±0.98 vs 4.54±2,82;t values:4.89,4.82,both P< 0.05),but it was still higher in benign breast lesions(SUVmax:2.37±1.62,SUVmean:1.50±0.92;t val-ues:2.35,2.29,both P<0.05).Also,target/non-target(T/NT)of 18F-Alfatide II in breast cancer lesions was higher than that in benign breast lesions(5.32±3.08 vs 2.60±2.37;t = 2.72,P<0.05).Condusion The biodistribution of 18F-Alfatide II in patients is favorable and 18F-Alfatide II can be clinically used for breast cancer imaging.

Preclinical microPET imaging in tumor-bearing nude mice and pharmacokinetic studies of 18F-Alfatide II / 中华核医学与分子影像杂志

Objective To assess the imaging characteristics of 18F-Alfalide II in different tumorbearing mice and pharmacokinetics in Beagle dogs.Methods BALB/c nude mice(n-24)were used for subcutaneous tumor models(A549 and U87MG),orthotopic lung cancer models(A549)and orthotopic breast cancer models(MDA-MB-231)(n=6 in each group).18F-Alfatide II and 18F-fluorodeoxyglucose(FDG)microPET/CT images were compared in the 4 types of tumor-bearing nude mice models.18F-Alfatide II blocking experiment,biodistribution experiment and imaging studies in tumors of different growth cycles were performed in A549 subcutaneous tumor-bearing nude mice models.Pharmacokinetic experiments were carried out in Beagle dogs(n = 6)and CD-1 mice(n = 9).Two-sample t test was used to analyze the data.Results Compared with 18F-FDG,18F-Alfatide II microPET/CT images showed better imaging quality and contrast in subcutaneous A549,U87MG tumors and orthotopic A549(tumor/heart:4.50±1.17 vs 0.95±0.31;t = 4.125,P<0.01),orthotopic MDA-MB-231(tumor/muscle:6.60±1.53 vs 0.92±0.43;t = 3.984,P<0.01)transplantation nude mice models.18F-Alfatide II could specifically target A549 tumors,and the tumor uptake of 18F-Alfatide II was reduced by about 75% after pre-injection with cyclo(Arg-Gly-Asp-D-Tyr-Lys)(c(RGDyk)).18F-Alfatide II was rapidly cleared from the blood of Beagle dogs(T1/2 was(57.34±11.69)min).It was cleared in the form of prototype drug and(69.24±6.82)% of cumulative dose was excreted through the urine within 4 h after administration.Conclusions 18F-Alfatide II shows a higher target/non-target ratio than,18F-FDG in the imaging of A549,MDA-MB-231 and U87MG tumor-bearing nude mice models,which is more conducive to the diagnosis of tumor.18F-Alfatide II has excellent pharmacokinetic properties.

18F-Alfatide n automated preparation based on 18 F-minireactor and microPET/CT imaging in tumor / 中华核医学与分子影像杂志

Objective To develop the automated preparation of 18F-Alfatide II using newly-designed 18F-minireactor and perform 18F-Alfatide D microPET/CT imaging in tumor.Methods The automated preparation of 18F-Alfatide H was developed by using 18F-microreactor and water phase Al18F-chelating method,and the radiochemical yield and quality analysis were measured.The nude mice bearing breast tumor ZR-75-1 and nasopharyngeal tumor CNE1 were established(n = 3 respectively).MicroPET/CT imaging was performed at 0.5,1.0 and 2.0 h after the injection of 18F-Alfatide II.The region of interest(ROI)was depicted and the tumor/muscle(T/M)ratio was calculated.Results 18F-Alfatide II was automatically prepared with the total synthesis time of 40 min,the radiochemical yield of(28±6)%(no decay corrected,n=11),and the radiochemical purity >97%.All quality analysis indexes accorded with the radiopharmaceutical requirements.18F-Alfatide II microPET/CT images of ZR-75-1 and CNE1 tumors were clear due to the high radioactivity uptake of tumor lesions(T/M ratio was greater than 4.0 at 1.0 h after injection).Conclusion Based on the 18F-minireactor,the,8F-Alfatide II can be prepared successfully with short synthesis time and high radiochemical yield,which can help the application studies in 18F-Alfatide II microPET/CT imaging.

Synthesis and biological evaluation of 18F-AlF-NOTA-c (CGRRAGGSC) / 中华核医学与分子影像杂志

Objective To synthesize 18F-AlF-1,4,7-triazacyclononane-l,4,7-triacetic acid (NOTA)-c (CGRRAGGSC),which could specifically bind to the α chain of interleukin (IL)-11 receptor (IL-11 R),and evaluate its targeting potential to IL-11 R-positive tumors.Methods Polypeptide c (CGRRAGGSC) was first coupled with NOTA and then labeled with 18F by AlF labeling method.The radiochemical purity and radiochemical yield of 18F-AlF-NOTA-c(CGRRAGGSC) were analyzed by high performance liquid chromatography,and the stability in vitro was evaluated.The tracer biodistribution in tumor-bearing mice (cell line SKOV3) was evaluated by the dynamic imaging with microPET 30 min,1 h,2 h after injection of 18F-AlF-NOTA-c (CGRRAGGSC).The tracer kinetics was performed in normal mice.Pharmacokinetics parameters were calculated using DAS2.0 software.Results The radiochemical purity of 18F-AlF-NOTA-c(CGRRAGGSC) was higher than 95％ and the radiochemical yield was (30.0±7.4)％.It could be stably maintained in phosphatebuffered solution and plasma for at least 2 h.MicroPET imaging showed that 18F-AlF-NOTA-c(CGRRAGGSC)had a good affinity to SKOV3 tumor.The tumor/muscle ratios at 30 min,1 h,2 h after the injection of 18F-AlF-NOTA-c(CGRRAGGSC) were 6.26±2.98,7.19±3.63 and 9.05±4.30,respectively.The tracer was cleared rapidly in blood and mainly excreted by the liver and kidneys.The T1/2α and T1/2β were (0.38±0.14) h and (2.64±0.28) h,respectively.Conclusions 18F-AlF-NOTA-c(CGRRAGGSC) is easy to be synthesized and has a good affinity to IL-11R-positive tumors.It will be a potential IL-11R-targeting imaging agent.

Application of wrist MRI combined anti-cyclic citrullinated peptide antibody detection in the diagnosis of early rheumatoid arthritis / 中国医师杂志

Objective To study the clinical value of wrist magnetic resonance imaging (MRI) combined anti-cyclic citrullinated peptide antibody detection in the diagnosis of early rheumatoid arthritis (RA).Methods Forty five patients with early RA were selected as RA group,45 cases of patients without rheumatoid arthritis as non-RA group,and 43 cases of people with normal examination as control group.All subjects were given wrist MRI and anti-cyclic citrullinated peptide (CCP) antibody with the enzyme linked immunosorbent assay (ELISA).At the same time,clinical symptoms,physical signs,MRI manifestations,and laboratory indicators were collected.All results were statistically analyzed.Results Positive rate of MRI lesions and serum anti-CCP antibody in RA group were significantly higher than non-RA group and control group (P ＜0.05).The sensitivity and specificity of MRI (or anti-CCP antibody) for early RA were 88.88％ and 82.22％ (or 68.88％ and 91.11％).The sensitivity (64.44％) of MRI combined with anti-CCP antibody was decreased compared to individual; however,the specificity (100％) of MRI combined with anti-CCP antibody was increased.The correlation of MRI synovial scores and anti-CCP antibody levels was positively correlated (rs =0.612,P ＜ 0.05).MRI abnormal signs and joint disease activity score (DAS28) were positively correlated (rs =0.521,P ＜ 0.05).Anti-CCP antibody levels and DAS28 were positively correlated (rs =0.541,P ＜ 0.05).Conclusions MRI examination and combined with anti-CCP antibody detection is helpful to improve the diagnosis of early RA,and it provides a detection basis for dynamic assessment of RA condition changes.

The features of patients with cyclic citrullinated peptide antibodies in primary Sj(o)gren's syndrome / 中国医师杂志

Objective To investigate the features of patients with cyclic citrullinated peptide (CCP) antibodies in primary Sj(o)gren's syndrome (pSS) with the retrospective method.Methods Seventy eight pSS patients were studied.Enzyme-linked immunosorbent assay (ELISA) indirect immunofluorescence was used to measure anti-CCP antibodies.The patients with and without anti-CCP antibodies were correspondingly classified as autoantibody-positive and negative pSS groups.Clinical and laboratory features were compared between autoantibody-negative and positive group.Results (1) Seven (9.0％) of pSS patients had positive anti-CCP antibody.No significant difference was found in sex,ages,and disease course between autoantibody-nagative and positive pSS patients.(2) The anti-CCP-positive pSS was associated with the rates of decayed tooth,fatigue,dry mouth,dry eyes,and tender of joint (P ＜ 0.05).Whereas,the antiCCP-negative pSS was not significantly related to fever and mumps (P ＞ 0.05).(3)From serologic characteristics aspects,the anti-CCP-positive patients showed higher level of tender of joint than the anti-CCP-negative patients.No significant difference was found in white blood cell (WBC),hemoglobin (HGB),platelet (PLT),erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),immunoglobulin A (IgA),IgG,IgM,and rheumatoid factor (RF) between two groups (P ＞ 0.05).Conclusions The anti-CCP-positive patients were 9％ ofpSS patients,and were more likely to occur tender of joint with higher level of tender of joint.

Distribution and significance of IgG subclasses of anti-CCP antibodies in sera from patients with rheumatoid arthritis / 中华检验医学杂志

Objective To evaluate the distribution and significance of IgG subclasses of anti-cyclic cirullinated peptide antibody (anti-CCP) in sera from patients with rheumatoid arthritis (RA).Methods A total of 83 patients with RA at the Department of Endocrinology of Taizhou Hospital , 51 disease controls and 50 healthy controls during the period from August 2012 to June 2013 were enrolled.The total serum IgG and IgG subclasses of anti-CCP antibodies were detected by antigen specific enzyme linked immune-sorbent assay( ELISA ).The prevalence and relative amount of IgG subclasses were calculated and compared.Statistical analysis was performed by χ2 test and Kruskal-Wallis H test.Results The positive rates of IgG subclasses of anti-CCP were anti-IgG 71.1%(59/83), anti-IgG1 78.3%(65/83), anti-IgG2 26.5%(22/83), anti-IgG3 60.2%(50/83), anti-IgG4 74.7%(62/83) respectively.The diagnostic value of anti-CCP-IgG1, anti-CCP-IgG3 and anti-CCP-IgG4 alone or combined (AUC =0.818-0.901),compared with anti-CCP-IgG(AUC=0.857), had no significant difference(Z=0.028-0.045,P>0.05).The DAS28 score of anti-CCP-IgG1(DAS28 =6.5), and anti-CCP-IgG4(DAS28 =6.5)positive in patients with RA were significantly higher than those in negative groups (DAS28=4.5,4.6)(U=396.0,427.5,P<0.01).The T28(T28=4.0,4.0)and SW28(SW28=4.0,4.0) results of CCP-IgG1and CCP-IgG4 positive in patients with RA were significantly higher than those in negative groups (T28=3.0,3.0,SW28 =3.0,3.0)(U=377.5,406.0,255.5,286.5,P<0.05).Conclusions The distribution of IgG subclasses of anti-CCP in sera from patients with RA was predominantly anti-CCP-IgG1, anti-CCP-IgG3 and anti-CCP-IgG4 associated with RA disease activity.However , whether joint detection of IgG subclasses can replace conventional anti -CCP is questionable.

Application of combined detection of anti-CCP, RF, and AKA in the diagnosis of rheumatoid arthritis / 中华检验医学杂志

Objective To investigate the application of combined detection of three serum markers,anti-cyclic citrullinated peptide antibody (anti-CCP),rheumatoid factor (RF),anti-keratin antibodies (AKA),for the diagnosis of rheumatoid arthritis.Methods This was a prospective study.Serum samples were randomly obtained from 137 RA patients,265 other autoinmmune diease patients,and 111 normal controls.All of the volunteers were outpatients or inpatients of Peking University Third Hospital from January 2011 to September 2013.Levels of AKA,anti-CCP antibody,RF were measured by indirect immunofluorescence,chemiluminescence,and immune turbidimetry,respectively.The values of 3 serum biomarkers and their varied combinations for RA diagnosis were systemically assessed.The results were compared using fourfold table chi-square (x2) test.Results When using one serum marker,anti-CCP had the highest accuracy (80.39％),Youden's index (YI) (0.51),and Kappa (κ) value (0.55) for the diagnosis of RA.While using three serum markers,anti-CCP + (AKA/RF),AKA /(anti-CCP + RF),anti-CCP/(AKA + RF) and (AKA + RF)/(anti-CCP + RF)/(AKA + anti-CCP) had the highest accuracy (80.94,80.94,80.66),YI (0.51,0.51,0.50),and κ value (0.55,0.56,0.54).Conclusion AntiCCP is the vital marker for RA diagnosis.Anti-CCP + (AKA/RF),AKA/(anti-CCP + RF),and (AKA +RF)/(anti-CCP + RF)/(AKA + anti-CCP) are the most ideal combinations for RA diagnosis.

Diagnostic value of anti-MCV antibodies for ankylosing spondylitis / 中华检验医学杂志

Objective To investigate the diagnostic value of anti-mutated citrullinated vimentin (anti-MCV) and anti-cyclic citrullinated peptide (anti-CCP) antibodies for ankylosing spondylitis (AS), and to establish a new diagnostic method of AS based on anti-citrullinated protein/peptide antibodies (ACPAs) detection.Methods Totally 121 AS patients(AS group), 97 rheumatoid arthritis(RA) patients (RA group)and 103 healthy people(control group) were enrolled for the detection of serum levels of anti-MCV and anti-CCP antibodies using ELISA method as a diagnostic test .HLA-B27 in AS patients was tested by flow cytometry , and RF-IgM in RA and AS patients was detected by immune rate nephelometry .Receiver operating characteristics ( ROC) curve was used to analyze the diagnostic value and to determine the cut-off value.Anti-MCV and anti-CCP antibodies among each group were compared by Mann-Whitney U test, Chi-square test or Fisher′s exact test was used to compare positive rate .Results The anti-MCV levels in AS group [11.60 ( 12.36-25.83 ) U/ml ] were significantly higher than control group [ 11.60 ( 8.41 -13.54)U/ml ],U=2 413,P <0.001, while the levels of anti-CCP had no difference between the two groups [AS group 6.22 (4.30 -8.07) U/ml], and control group [6.01 (3.77 -7.58) U/ml], respectively;U=5 421,P=0.094.The calculated area under the ROC curve of anti-MCV was 0.806,and 14.67 U/ml was the optimal cut-off value with sensitivity of 0.645 and specificity of 0.942.In both HLA-B27 positive and negative AS patients , anti-MCV antibodies levels and positive rate were significantly higher than control group using new cut-off value above (U =133.5, P =0.001; U =2 279.5,P <0.001). Sensitivity of the combination detection of anti-MCV and anti-CCP ( MCV+CCP-) or RF-IgM ( MCV+RF-) were 60.3%(73/121), 62.8% (76/121) and specificity were 89.7% (87/97), 90.7% (88/97) respectively in differential diagnosis of AS and RA , which were significantly higher than anti-MCV detection alone in specificity (16.5%,16/97).Conclusions Anti-MCV could be a new biomarker for the diagnosis of AS .With high sensitivity and specificity , anti-MCV has an equal diagnostic efficiency in HLA-B27 positive and negative AS patients using our new cut-off value.Additionally, the combination detection of anti-MCV and anti-CCP or RF-IgM could be an effective method for differential diagnosis of AS and RA .

Clinical relevance of anti-CCP antibody in the clinical testing / 中华检验医学杂志

As a kind of common autoimmune diseases,rheumatoid arthritis (RA) affected the health of human beings seriously.In the past,serological diagnosis of RA solely relied on the detection of rheumatoid factor (RF),but its specificity was not satisfactory.Lately,people found that anti-cyclic citrullinated peptide (CCP) antibody was a serological indicator of RA.Now,there have been a series of kits for the detection of anti-CCP antibodies to diagnose RA.The sensitivity and specificity of anti-CCP antibody detection are better than those of RF detection.This paper reviews the significance and value of anti-CCP antibody detection used for clinical diagnosis in the recent years,while systematically compares the sensitivities and specificities between several common commercial kits and methods of anti-CCP antibodies detection.

Direct inhibitory effects of 153Sm-DTPA-c(CGRRAGGSC) on human prostate cancer PC-3 cells / 中华核医学杂志

Objective To investigate the direct inhibitory effects of 153Sm- DTPA-c (Cys-Gly-Arg-Arg-Ala-Gly-Gly-Ser-Cys) NH2 ( 153 Sm-DTPA-c (CGRRAGGSC)) on human prostate cancer PC-3 cells. Methods 153Sm-DTPA-c(CGRRAGGSC) was synthesized by the reaction of 153SmCl3 with DTPA-c(CGRRAGGSC) using indirect synthesis method. PC-3 cells in vitro culture were divided into four study groups, groug A ( the control, with PBS only), group B with 1.5 mg/L c ( CGRRAGGSC), group C with 370 kBq 153 SmCl3 and group D with 370 kBq 153Sm-DTPA-c(CGRRAGGSC). PC-3 cell growth was assayed by 3-(4, 5-dimethylthiazol-2-yl ) -2, 5-diphenyltetrazolium bromide (MTT) method. Cell cycle and apoptosis were analyzed by flow cytometry. The expression changes of interleukin 11 (IL11 ) and IL11 receptor (IL1 1 R) in PC-3 cells were examined by Western Blot. One way analysis of variance (ANOVA) and paired-t test were applied for statistic analysis. Results The labeling yield of 153Sm-DTPA-c (CGRRAGGSC) was 85% and the radiochemical purity was 95.8%. The specific activity of 153Sm-DTPA-c(CGRRAGGSC) was 1.32 × 105 MBq/μmol. Significant inhibitory effects on the growth of PC-3 cells were found in both group C and D, with a time-dependent manner. However, no obvious inhibition was found either in group A or in group B. After 48 h,significant differences of sub-G1 peak area were found among groups, (0. 98 ± 0. 18)%, (0. 35 ±0. 10)%, (4.05 ±0.28)% and (13.38 ±0. 89)% for group A, B, C and D, respectively. Furthermore,sexpression of ILl 1R in group D was significantly lower than that in group B and C with absorbance values 0. 339 ~ 0.014, 0.338 ~ 0.019, 0.226 ~ 0. 015 for group B, C and D, respectively. Absorbance values in groups B and C were not significantly different after treatment, compared with those before treatment; however, there was difference between absorbance values after and before treatment in group D ( t = 0. 405,1. 163,135.989,P>0.05 >0.05, <0.05). Conchluion 153Sm-DTPA-c(CGRRAGGSC) can directly in hibit the cell growth and expression of human prostate cancer cells PC-3.

Efficacy and safety of micafungin in the treatment of invasive fungal infections in patients with acute leukemia / 中华传染病杂志

Objective To evaluate the efficacy and safety of micafungin in the treatment of invasive fungal infections (IFI) in patients with acute leukemia.Methods A total of 133 IFI patients with acute leukemia received micafungin 150 mg once daily for 14 days.The clinical and mycological efficacies were evaluated on (7±2) days and(14±2) days of treatment.Meanwhile,the adverse events were recorded.The normally distributed data was compared using analysis of variance and nonnormal distributed data was analyzed using Wilcoxon rank-sum test.Results Among 133 IFI patients with acute leukemia,116 finished the 14-day micafungin treatment.The total clinical efficacy was 94.8% and the total mycological efficacy was 75.0% at (14±2) days of treatment.The fungus eliminate rates were 82.9%,66.7% and 55.6% against Monilia,Aspergillus and others,respectively.The clinical and mycological efficacies of (14±2)-day treatment were both higher than those of (7±2)-day treatment(X2=6.060,34.416.both P<0.05).The clinical efficacy was not related with age,sex,IFI diagnose,types of leukemia and combinative drugs (X2=26.541,P<0.05).The incidence of drug-related adverse events of micafungin was 3%among 133 patients,which included skin rash in 3 eases, diarrhea in 1 case. Only one case was discontinued because of severe skin rash and micafungin was well tolerant in other patients. Conclusion Treatment of micafungin 150 mg daily for 14 days is effective and safe in IFI patients with acute leukemia.

A novel 99Tcm labelled polypeptide analogue for interleukin-11 receptor imaging in a bone metastases model for prostate cancer / 中华核医学杂志

Objective To assess the feasibility of a novel 99Tcm labelled polypeptide analogue for interleukin-11 receptor ( IL11R) imaging in a bone metastases model for prostate cancer. Methods A novel circular polypeptide analogue of IL11 ( c( CGRRAGGSC ) ) was indirectly labeled with 99Tcm and the product was named as 99Tcm-DTPA-IL11 RR. The labeling efficiency, radiochemical purity and stability of the product were measured with paper chromatography and high performance liquid chromatography (HPLC). The biodistribution of 99Tcm-DTPA-IL11RR was investigated in 28 ICR normal mice. The organ radioactivity was measured as percentage activity of injection dose per gram of tissue ( %ID/g). The models of bone metastases from prostate cancer were established at the tibias of BALB/c nude mice bearing human prostate cancer PC-3 cells. The tumor bearing ( n= 5 ) and standard closed fracture nude mice models underwent both 99Tcm-DTPA-IL11RR and 99Tcm-methylene diphosphonate (MDP) scintigraphy study. The images were acquired at 0.5, 1,2, 4, 6, 8, 24 h after intravenous injection of the tracers. The competitive inhibition imaging was perfomed in three tumor bearing mice. One-way variance analysis was used. Results The labeling efficiency was 90.7%. The radiochemical purity of 99Tcm-DTPA-IL11RR in normal saline solution was (99.57 ±0.09)%, (99.29 ±0.18)%, (98.95 ±0.78)%, (98.67 ±0.11)%, (96.53 ±0.91)%, (95.20±0.70)%, (88.38 ±0.22)% and (36.17±1.29)% at room temperature after0, 1,2, 3, 4, 6, 8 and 24 h, respectively. The tracer radiochemical purity in the blood of ICR mice remained over 90% at 37 C for 6 h. The labeling compounds were excreted mainly through kidney. The peak uptake of bone ( ( 1.910 ±0.109) %ID/g) and liver ( (0.366 ±0.030) %ID/g) was at 4 h after injection. In the tumor bearing mice, the uptake of spine marrow and large joints of extremities was mild. The highest uptake at tumor region was at 4 h and persistent at 6-8 h after injection. The tumor to non-tumor ratios (T/NT) were 1.17 ±0.17, 2.20 ±0.29, 3.20 ±0.15, 3.67 ±0.23, 13.61±0.85, 9.45 ±0.37 and 3.33 ±0.30 at 0.5,1, 2, 4, 6, 8 and 24 h, respectively (F=621.54, P＜0.05). In the standard closed fracture models,high uptake of 99Tcm-MDP was shown at the fracture site, with no increased 99Tcm-DTPA-IL11RR uptake noted. The tumor uptake was significantly depressed after a pre-injection of the unlabeled polypeptide analogue. Conclusions The synthesis of 99Tcm-DTPA-IL11RR is stable and the labeling efficiency is high. It may be a potential molecular probe in metastatic bone imaging for prostate cancer.

Evaluation and detection of CCP antigen-specific T cells by ELISpot assay in patients with rheumatoid arthritis / 中华检验医学杂志

Objective To optimize and establish ELISpot assay for CCP/AST which could secrete IFN-γ and IL-4, and explore the role and clinical significance of CCP/AST cells in occurrence and development of RA disease. Methods CCP was used as specific-stimulator with FLAG peptide as a control,the frequencies of positive SFC which could specifically secrete IFN-γ and IL-4 in 64 cases of RA, 64 cases of non-RA autoinunune diseases and 30 cases of healthy individuals were tested by ELISpot technique. The diagnostic value of CCP/AST cells was evaluated in patients with RA disease. Meanwhile, the relationships among the indexes above and patient joint symptoms as well as other laboratory parameters were further analyzed and discussed. Results The results showed that the mediam numbers of IFN-γ-SFC and IL-4-SFC were 39(12-77)/3 x 105 PBMC and 1 (1-3)/3 × 105 PBMC in RA patients, the positive rates were 81.3% and 18. 8% respectively. The median value of IFN-γ-SFC/IL-4-SFC ratio was of 15(5-39), the positive rate was of 78. 1%. Both IFN-γ-SFC and ratio of IFN-γ-SFC/IL-4-SFC were significantly higher than those of non-RA diseases (Z = - 7. 458, - 7. 019, P < 0. 01 ) and healthy control ( Z = - 6. 643, - 5. 760, P <0. 01 ), also both these parameters in RA patients with positive anti-CCP antibody and negative anti-CCP antibody were significantly higher than those patients with systemic lupus erythematosns ( Z = - 6. 573, - 6. 098, - 4. 552, - 4. 726, P < 0. 01 ), ankylosing spondylitis ( Z = - 3. 520, - 3. 326, - 2. 950,-2. 126, P<0. 01 or 0. 05), other autoimmune diseases (Z = -4. 838, -4. 418, - 3. 681, -3. 839,P < 0. 01 ) and healthy controls ( Z = - 6. 553, - 5. 578, - 4. 635, - 4. 163, P < 0. 01 ). Combining IFN-γ-SFC, IL-4-SFC with IFN-γ-SFC/IL-4-SFC for RA diagnosis, the area under curve of receiver operating characteristic( ROCAUC) and Youden index were 0. 910 and 0. 747. The diagnostic sensitivity and specificity were 87. 5% and 87.2%. Positive and negative predictive values were 82. 4% and 91.1%, respectively. Correlation analysis showed that ratio of IFN-γ-SFC/IL-4-SFC was not only significantly correlated with antiCCP antibody(r =0.393, P <0.01), but also correlated with joint symptoms in patients such as with number of joints swelling-pain ( r = 0. 429 , P < 0. 01 ), number of joints damage ( r = 0. 463, P < 0. 01 ),rheumatoid factor (r = 0. 166, P < 0.01) and erythrocyte sedimentation rate (r=0. 199,P<0.05).Conclusions There is widely existence of CCP/AST cells activation and abnormity in RA patients,indicating higher frequency of CCP-specific Th1 cells. These results provides a new experimental evidence for an objective understanding the function of specific cellular immune responses and cytokine network regulation mediated by citrullinated proteins in RA. So, the assay for CCP/AST cells has potential values in RA diagnosis and clinical application.

Imaging of 99Tcm-cycllc RGD tetramer in nude mice bearing U87MG human glioma xenografts / 中华核医学杂志

Objective Multimeric cyclic RGD (Arg-Gly-Asp) peptides are capable of improving the integrin αvβ3-binding affinity due to the polyvalence effect.In this study,the authors prepare 99Tcm-la-bearing cyclic RGD tetramer E{E[c(RGDfK)]2}2,and evaluate its biodistribution and imaging in nude mice beating U87 MG human glioma xenografts with integrinαvβ3-positive.Methods 99Tcm-hydrazino-nictinamide (HYNIC)-E{E[c(RGDfK)]2}2 was prepared by two-step method,while HYNIC wag chosen as bifunctional chelator,and tricine and trisodium triphenylphosphine-3,3,3-trisuifonate (TPPTS) as coligands.The af-finity of c (RGDyK) monomer,HYNIC-E[c(RGDfK)]2 dimer and HYNIC-E{E[c(RGDfK)]2}2 tetramer to integrin αvβ3 was compared by in vitro competitive assay against binding of 125I-c(RGDyK)to integrin αvβ3.positive U87 MG human glioma cells.The biodistribution [the percentage of injection dose per gram of tissue(%ID/g)] and imaging were performed in nude mice bearing UB7MG human glioma xenografts.Re-suits The labeling yield of 99Tcm-HYNIC-E{E[c(RGDfK)2}2 was over 95%,and the radiochemical purity was more than 99%after purification with Sop-Pak C18 cartridge.The 50%inhibiting concentration (IC30) val-ues of c(RGDyk),HYNIC-E[c(RGDfK)]2 and HYNIC-E{E[c(RGDfK)]2}2 were 85.9,9.5 and 4.5 nmol/L, respectively.The result indicated that RGD tetramer possessed a significantly higher affinity to in-tegrinαvβ3.The biodistribution data showed that 99Tcm-HYNIC-E{E[c(RGDfK)]2}2 was excreted mainly through kidneys.The tumor uptake of 99Tcm-HYNIC-E{E[c(RGDfK)]2}2 was two times higher than 99Tcm- HYNIC-E[c(RGDfK)]2,at 1h postinjection,with the uptake of(10.32±0.07)%ID/g and(5.15±0.52)%ID/g,respectively,which was consistent with the in vitro competitive binding data.The tumor up-tale of 99Tcm-HYNIC.E{E[c(RGDfK)]2}2 was still as higher as(9.35±1.35)%ID/g at 4 h postinjec-tion, which demonstrated that the retention time of radiotracer in tumor was long enough.The imaging showed that tumor was clearly visualized at 1h postinjection,and the image at 4 h postinjection Was better.Conclusion The higher tumor uptake and longer retention time in tumor make 99Tem-HYNIC-E{E[c(RG-DfK)J 2}2 a promising radiotracer for integrinαvβ3-positive tumors imaging,furthermore,suggest that radi-onuelides(such as 90Y).1abeled RGD tetramer is more suitable for the therapy of integrin αvβ3-positive tumors.