Objective To investigate the effect of 188Re-IGF-1 analogue (IGF-1A) in proliferation inhibition and apoptosis induction in human pancreatic carcinoma cell line Patu8988.Methods IGF-1A was labeled with 188Re.Patu8988 cells were divided into an un-treated control group,IGF-1A group (1,5,10,20 μg),188ReO4-group (0.37,1.85,3.70,7.40 MBq) and 188Re-IGF-1A group (0.37,0.74,1.85 MBq).The cell proliferation inhibition effects by the 188Re-IGF-1A and 188ReO4-were detected every day by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test from 1 d to 7 d after administration,while the IGF-1 A group was tested every day from 1 d to 6 d after treatment.Inhibition rates were calculated.At 3 d after treatment with 188ReO4-and 188Re-IGF-1A (1.85,3.70,7.40 MBq),cell apoptosis was detected by flow cytometry.For biodistribution studies of 188Re-IGF-1A,36 nude mice bearing Patu8988 cell xenografts were divided into6 groups.At different time points (15 min,1 h,4 h,1 d,3 d and5 d),36 mice (n =6 per time point) were sacrificed and organs of interest were removed,weighted and measured for radioactivity by a gamma counter.The absorbed doses of organs were calculated as ％ ID/g.One-way analysis of variance was used.Results After 4 d,inhibition rate of Patu8988 cell proliferation in the 188 Re-IGF-1A group (1.85 MBq) was (90.75 ±5.20) ％,higher than that in 188ReO4-group or IGF-1A group ((49.50±2.39)％,(23.00±4.21)％; F=554.724,P＜0.01).At 3 d after treatment with different doses of 188 Re-IGF-1A (1.85,3.70,7.40 MBq),floating cell ratios were (16.56 ± 0.95) ％,(33.39 ±5.93) ％ and (43.76 ± 1.38) ％,respectively.Apoptosisratios in the floating cells treated by 188 Re-IGF-1A (1.85,3.70,7.40 MBq) were (12.70±2.27)％,(17.80±1.51)％ and (23.23 ±1.22)％,respectively.Distribution in tumors was (39.30 ± 17.98),(10.59 ± 9.39),(5.32 ± 1.53) and (5.30 ±2.28) ％ ID/g at the 15 min,1 d,3 d,and 5 d timepoints after intratumoral injection,respectively.The absorbed dose of tumors was 5165.8 mGy/MBq.Conclusions Proliferation of human pancreatic carcinoma cell line Patu8988 can be inhibited and apoptosis can also be induced by 188Re-IGF-1A.The tumor region is the major distribution site in nude mice bearing human pancreatic cancer xenografts after intratumoral injection of 188 Re-IGF-1A.

Objective To evaluate the effect of P-gp inhibitors of verapamil (VER) and GF120918 on 18F-FDG uptake in Bcap37 and Bcap37/multidrug resistancce (MDR)1 cell lines in vitro,and to explore the relationship between 18F-FDG uptake and P-gp expression at cellular level.Methods Bcap37 and Bcap37/MDR1 cells were seeded into 6-well plates at a density of 1 × 106 per well.Three days later,37 kBq/ml 18F-FDG,or 37 kBq/ml 18F-FDG + 100 μmoL/L VER,or 37 kBq/ml 18F-FDG + 50 μmol/L GF120918 were added into each well.Mter incubated for 10,30,60 and 120 min at 37 ℃ and in 5％ CO2,the medium was removed and the cells were washed three times with 1 ml ice-cold PBS immediately.The radioactivity of 18 F-FDG was measured using a gamma counter.The uptake of 18F-FDG was expressed as the ratio of 18F-FDG radioactivity in Bcap37 or Bcap37/MDR1 cells and the overall radioactivity added to the cells in each well.The t test was used for statistical analysis.Results 18F-FDG uptake was higher in Bcap37/MDR1 cells than that in Bcap37 cells after incubated for 10 min.The uptake rate was (1.88 ±0.19) ％ in Bcap37/MDR1 cells and (1.37 ± 0.18) ％ in Bcap37 cells (t =7.832,P ＜ 0.05).On the contrary,18 F-FDG uptake was significantly higher in Bcap37 cells than that in Bcap37/MDR1 cells after incubated for 60 and 120 min.The uptake rates were (2.29 ±0.23)％ and (2.34 ±0.15)％ in Bcap37 cells,(1.47 ±0.14)％ and (1.53 ±0.22)％ in Bcap37/MDR1 cells (t =8.437,8.283,both P ＜ 0.05).18 F-FDG uptake was significantly higher with VER or GF120918 in Bcap37/MDR1 cells than that without VER or GF120918 after the incubation of 60 and 120 min (t =9.032,9.243 and 8.765,8.803,all P ＜ 0.05).The uptake rates with VER or GF120918 were (2.45 ±0.21)％ and (2.46 ±0.25)％,(2.50 ±0.24)％ and (2.48 ±0.27)％.There was no significant difference of 18F-FDG uptake in Bcap37 cells with or without VER or GF120918.Conclusions 18F-FDG is a substrate of P-gp at cellular level.P-gp may act as an efflux pump to reduce 18F-FDG uptake in Bcap37/MDR1 cells.The uptake of 18F-FDG can be used to evaluate the function of P-gp in tumor cells.

Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice.Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice (1× 107cells/ml,0.2 ml/mouse) to construct mice models.Bcap37 (n=5) or Bcap37/MDR1 (n=5) tumor-bearing mice fasted for 6 h before imaging.After anesthesia,the mice were injected with 7.4 MBq of 18F-FDG via tail vein.The dynamic microPET scans were carried out for 90 min.On the microPET images,the ROI was drawn and the TAC was obtained.The next day,those 10 mice underwent dynamic microPET scans after injected with elacridar (GF120918) and 18F-FDG.Another 10 mice,5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors,were used.After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein,microPET images were acquired at 60 min.ROI was drawn over the tumors and SUV was obtained.Two-sample t test was used to analyze the data.Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors,but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors.GF120918 did not influence 18F-FDG uptake (SUV) in Bcap37 tumors (1.052±0.028,1.028±0.045,t =1.792,P＞0.05),but significantly increased the SUV in Bcap37/MDR1 tumors (1.015±0.043,0.712±0.031,t=3.365,P＜0.05);The SUV of 18 F-FDG in Bcap37 tumors was significantly higher than that in Bcap37/MDR1 tumors without injection of GF120918 (t =3.952,P＜0.05).The SUV was not significantly different when GF120118 was injected (t=1.835,P＞0.05).Conclusions 18F-FDG is a substrate of P-gp.18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor's MDR.

Objective To evaluate the capability of 18 F-FLT uptake and investigate the early radiation response of human colorectal cancer cells HCT116 exposed to 6 MV X-rays.Methods 3.7 kBq 18F-FLT was added to HCT116 cells with different cell numbers (1.0 × 105-1.5 × 106) and cultured with different times (36,60,84 h).The 18F-FLT uptake rate was measured with a γ-counter after exposed to different does of 6 MV X-rays (0,2,4,6,8 Gy) after 24,48,and 72 h of irradiation.Then the cell uptake inhibition rate,cell proliferation,and cell cycle phase were measured.Results The uptake rate of 18F-FLT in HCT116 was (18.97 ± 1.16)％.The 18F-FLT uptake inhibition rates at 24 h after different does of irradiation (2,4,6,8 Gy) were (32.10±0.02)％,(54.46 ±0.04)％,(62.74 ±0.04)％,and (65.81 ±4.81)％,respectively,which was positively correlated with radiation dose.Conclusions The 18F-FLT uptake rate of human colorectal cancer HCT116 cells could be used to evaluate the early radiation response.

Objective To investigate the relationship between the expression of ITGAV and the radiosensitivity of NSCLC cells. Methods The expression of ITGAV in NSCLC and its relationship to the prognosis of patients who received radiotherapy were analyzed using bioinformatics methods. Differences in radiosensitivity between radio-resistant cells and parent cells were verified by clone formation experiment, and the protein expression of ITGAV was detected by Western blot. The transfection efficiency of si-ITGAV was determined by Western blot and qRT-PCR analyses. The best ITGAV interference sequence was selected to transfect A549R and H1299R cells. Clone formation experiment and flow cytometry were used to detect clone formation, apoptosis and cell cycle of A549R and H1299R cells. Results The expression of ITGAV in NSCLC tissues was significantly higher than that in normal tissues (P<0.05), and NSCLC patients with high ITGAV expression had poor prognosis. The clonogenic ability of the si-ITGAV group was significantly lower than that of the negative control group at 4, 6, 8Gy irradiation (all P<0.05). After 6 Gy irradiation, the apoptosis of the si-ITGAV group was increased (P_H1299R<0.0001, P_A549R=0.0002), the proportion of G₂/M phase cells to A549-siITGAV and H1299R-siITGAV cells was higher than that in the negative control group (P_H1299R<0.0001, P_A549R=0.0007). Conclusion Interfering with ITGAV expression can increase the radiosensitivity of NSCLC.

Objective To establish the acquired tamoxifen (TAM)-resistant human breast cancer cell line T47D-TamR,compare the 18F-FDG uptake rate between T47D-TamR and its parental cell line T47D,and study the mechanism.Methods Long-term step-wise drug stimulation was used for cell line T47D-TamR establishment and then the cell proliferation and resistance index (RI) were determined by MTT assay.The 18F-FDG uptake rates of T47D-TamR and T47D cells were measured in the setting of different cell counts,reaction time,18F-FDG dosages and glucose concentrations.The LDH activity,cellular ATP level and lactic acid concentration in cell supernatant of T47D-TamR and T47D cells were detected.Western blot was used to examine the expression of ERα,Glut-1,phosphorylated AMPK (p-AMPK) and phosphorylated mTOR (p-mTOR).Two-sample t test and two-way analysis of variance were used to analyze the data.Results T47D-TamR cell line was successfully established and its drug RI was 1.97±0.08,with a significantly decreased cell proliferation efficacy (F =230.10,P＜ 0.05).Significant differences of 18 FFDG uptake rates were found between T47D-TamR cell and T47D cell when changing the cell count,reaction time,and 18F-FDG dosage (F values:419.00-1 116.00,all P＜0.05).The LDH activities of T47D cell and T47D-TamR cell were (0.42±0.04) and (0.32±0.02) U/mg protein,cellular ATP levels were (19.99±0.32) and (14.01±0.70) nmol/mg protein,lactic acid concentrations in cell supematant were (2.95±0.05) and (2.02±0.07) mmol/L,respectively.The differences of above parameters between the two groups were significant (t values:4.39-18.80,all P＜0.05).The relative expressions of ERα,p-AMPK,pmTOR,Glut-1 were 0.26±0.03,0.36±0.06,0.75±0.11,0.35±0.07 in T47D cell,and 0.17±0.02,0.61±0.09,0.52±0.08,0.21±0.04 in T47D-TamR cell,and there were significant differences (t values:12.20-16.45,all P＜0.05) between the two groups.Conclusions Compared with parental cells,T47D-TamR cells have lower 18F-FDG uptake rate,LDH activity,cellular ATP level and lactic acid concentration,increased p-AMPK expression and decreased ERα,p-mTOR,Glut-1 expression,indicating the decreased glycolysis ability in TAM-resistant breast cancer cells.

Objective To evaluate the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT before or after autologous hematopoietic stem cell transplantation (Auto-HSCT) in patients with non-Hodgkin's lymphoma (NHL).Methods Fifty-eight NHL patients who underwent PET/CT scan before or after Auto-HSCT were retrospectively analyzed.Between June 2007 and May 2016,40 patients (32 males,8 females;median age 39 years) underwent 18F-FDG PET/CT pre-transplantation,and 34 patients (23 males,11 females;median age 34 years) underwent 18F-FDG PET/CT post-transplantation.There were 16 patients underwent both pre-and post-transplantation imaging.PET/CT results were categorized as positive or negative according to the standard response criteria.The predictive value of PET/CT was evaluated with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis and logrank test.Three-year PFS and OS of different groups were compared with Fisher exact test.Results (1) 18 F-FDG PET/CT before Auto-HSCT:PFS of patients in PET/CT negative group (n =27) and positive group (n=13) were significantly different (x2=4.187,P＜0.05),3-year PFS was 63.6％(14/22) vs 1/7 (P=0.031).However,OS of the 2 groups were not significantly different (x2=1.777,P＞0.05).(2)18F-FDG PET/CT after Auto-HSCT:PFS and OS of patients in PET/CT negative group (n=18) and positive group (n =16) were significantly different (x2 values:15.430,7.726,both P＜0.01).The 3-year PFS and OS of the 2 groups were 8/10 vs 2/12(P=0.005) and 8/10 vs 4/12 (P=0.038),respectively.Conclusion 18F-FDG PET/CT before or after Auto-HSCT could provide prognostic information for NHL patients.

Objective To explore the effect of depression on loneliness in medical students',and the mediating effects of introverted personality and social support.Methods EPQ,UCLA,SSRS,and POMS questionnaire were used,and surveyed data was collected from Dalian Medical University medical students.Results The scores of depressive mood,introverted personality,social support and loneliness were (17.77±4.45),(11.97±5.21),(34.52±6.15) and (38.02±6.36).Depression was positively related to loneliness and introverted personality (r=0.286,0.508,P＜0.01),and social support was negatively related to loneliness (r =-0.443,P＜0.01).Introverted personality was positively related to loneliness(r=0.401,P＜0.01).The total effect value was 0.670.The mediating effect of introversion as mediator variable was 0.221,accounting for 33％ of the total effect.Social support as intermediary variable,intermediary effect value was 0.449,accounting for 67％ of the total effect.Standard value of mediating effect between depression and introverted personality showed as 0.508 (95％CI=0.475-0.725,P＜0.0i),standard value of mediating effect between depression and social support showed as-0.150 (95％CI=0.989-1.469,P＜0.01),introverted personality was the mediating variant of depression and loneliness,standard value of mediating effect was 0.156 (95％ CI=0.080-0.232,P＜0.01),social support was the mediating variant of depression and loneliness,standard value of mediating effect was 0.317 (95％ CI=0.177-0.457,P＜0.01).Conclusions Introverted personality and social support play an intermediary role between depression and loneliness.

OBJECTIVE: The purpose of this study was to prospectively investigate the value of the myocardial extracellular volume fraction (ECV) in predicting myocardial functional outcome after revascularization of coronary chronic total occlusion (CTO). MATERIALS AND METHODS: Thirty patients with CTO underwent cardiovascular magnetic resonance (CMR) before and 6 months after revascularization. Three baseline markers of functional outcome were evaluated in the dysfunctional segments assigned to the CTO vessels: ECV, transmural extent of infarction (TEI), and unenhanced rim thickness (RIM). At the global level, the ECV values of the whole myocardium with and without a hyperenhanced region (global and remote ECV) were respectively measured. RESULTS: In per-segment analysis, ECV was superior to TEI and RIM in predicting functional recovery (area under receiver operating characteristic curve [AUC]: 0.86 vs. 0.75 and 0.73, all p values < 0.010), and it emerged as the only independent predictor of regional functional outcome (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.77–0.89; p < 0.001) independent of collateral circulation. In per-patient analysis, global baseline ECV was indicative of ejection fraction (EF) at the follow-up examination (β = −0.61, p < 0.001) and changes in EF (β = −0.57, p = 0.001) in multivariate regression analysis. A patient with global baseline ECV less than 30.0% (AUC, 0.93; sensitivity 94%, specificity 80%) was more likely to demonstrate significant EF improvement (OR: 0.38; 95% CI: 0.17–0.85; p = 0.019). CONCLUSION: Extracellular volume fraction obtained by CMR may provide incremental value for the prediction of functional recovery both at the segmental and global levels in CTO patients, and may facilitate the identification of patients who can benefit from revascularization.
Collateral Circulation ; Coronary Vessels* ; Follow-Up Studies ; Humans ; Infarction ; Magnetic Resonance Imaging* ; Myocardial Infarction ; Myocardial Ischemia ; Myocardium ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity

Objective To examine the distribution,volume and glucose-uptake activity of brown adipose tissue (BAT) in adults and investigate their correlations with metabolic indicators.Methods 18F-flurodeoxyglucose (FDG) PET/CT was used to analyze the distribution,volume and glucose-uptake activity of BAT.The clinical and metabolic differences between BAT positive group (n =121) and BAT negative group (n=257) were compared.The influences of metabolic indicators (fast blood glucose (FBG),triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),uric acid (UA)) on the distribution,volume and activity of BAT were investigated.Logistic regression analysis,two-sample t test,x2 test and multiple linear regression were used to analyze the data.Results The distribution,volume and glucose-uptake activity of BAT were found to be significantly higher in subjects being tested in colder seasons than those who were tested in warmer seasons:2.91％ (87/2 991) vs 1.68％(34/2018),(433±402) vs (329±298) ml,(212±183) vs (169±145) g (x2=7.66,t values:3.36 and 2.98,all P＜0.05).The female proportion was significantly higher in BAT positive group than that in BAT negative group:68.60％ (83/121) vs 31.91％ (82/257) (x2 =16.10,P＜0.01).The average levels of age,body mass index (BMI),FBG,TG,TC,LDL-C and UA in BAT positive group were significantly low-er than those in BAT negative group:(41.30±10.90) vs (48.70±9.60) years,(21.30±2.40) vs (24.50± 3.10) kg/m2,(4.56±0.74) vs (5.34±1.33) mmol/L,(0.94±0.36) vs (2.06±1.64) mmol/L,(4.42± 0.79) vs (4.88±0.87) mmol/L,(1.99±0.58) vs (3.10±0.77) mmol/L,(285.11±70.00) vs (347.70± 101.10) μmol/L (t values:from-6.25 to-2.94,all P＜0.01).Logistic regression analysis revealed that season,gender,age,BMI,FBG,TG and LDL-C levels were all independent influencing factors of BAT distribution in adults (odds ratios:5.36,2.06,0.95,0.79,0.49,0.23,0.02;P＜0.01 or P＜0.05).Among BAT positive adults,gender and FBG levels were found to be strongly affected by the volume and glucose-uptake activity of BAT (β values:0.28,-0.21,both P＜0.05).Conclusions The distribution,volume and glucose-uptake activity of BAT in adults are associated with multiple metabolic indicators including BMI,levels of glucose,lipid and UA.The distribution of BAT is affected by gender,age,season,BMI,blood glucose,and blood lipids.