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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.
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Objective To synthesize 18F-AlF-NOTA-G-TMTP1 and evaluate its potential for PET imaging on nude mice bearing high-metastatic potential hepatoma cells.Methods NOTA-G-TMTP1 was synthesized by the standard Fmoc-solid phase synthetic protocols and radiolabeled with 18F using NOTA-AlF chelation method.The nude mice models bearing low-metastatic potential HCC97L and high-metastatic potential HCCLM3 xenografts were established separately.The tumor-targeting characteristics of 18F-AlF-NOTA-G-TMTP1 were assessed by microPET/CT and biodistribution assay.Results NOTA-G-TMTP1 was labeled with 18F in one step with (25±6)％ labeling yield (n=5).The radiochemical purity of 18F-AlF-NOTA-G-TMTP1 was more than 95％ with a specific activity more than 11.1 GBq/μmol.The octanol/water partition coefficient (logP) for 18F-AlF-NOTA-G-TMTP1 was-3.166±0.022.The tumor to muscle ratios were 1.8± 0.4 and 4.7±0.2 at 35 min post injection for HCC97L and HCCLM3,respectively.The uptake of 18F-AlF-NOTA-G-TMTP1 in HCCLM3 tumor was inhibited (61.4％) by unlabeled G-TMTP1.Conclusion 18F-AlF-NOTA-G-TMTP1 has been successfully synthesized.It shows specific uptake by tumor induced by the high-metastatic potential hepatoma cells.
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Objective To investigate the effects of acarbose versus fenofibrate on insulin secretion and insulin resistance in the subjects with impaired glucose tolerance (IGT) and hypertriglyceridemia. Methods Eighty subjects were allocated to acarbose group (28 cases),fenofibrate group (30 cases),and control group (22 cases) without intervention for 3 months,and also divided into elderly (46 cases) and younger groups (34 cases). Fasting blood samples were collected for measuring fasting plasma glucose and lipid.Oral glucose tolerance test (OGTT) were carried out with measurement of plasma insulin and glucose before ad after treatment.Early insulin secretion indexes(△I30/△G30),insulin secretion indexes (HOMA -β) and insulin resistance indexes (HOMA-IR)were calculated. Results After 3-months of treatment,the lipid profile was evidently improved in fenofibrate group. Levels of triglyceride (TG) and total cholesterol (TC) were significantly reduced ( both P ＜ 0.01 ),△I30/△G30 was significantly increased (P ＜ 0.05) and HOMA-IR was decreased (P＜＜0.01).In acarbose group,levels of fasting plasma glucose (FPG),2hours postprandial plasma glucose (2 hPG) and HOMA-IR were reduced (all P＜0.01),△I30/△G30 and HOMA-β were enhanced (P＜0.01 or P＜0.05).No change of above indicators was found in the control group.Compared with fenofibrate group,acarbose group had higher △ I30/△G30 (P＜ 0.05),HOMA-β (P＜ 0.01 ) and lower HOMA-IR ( P ＜ 0.01 ).The improvement of △△I30/△G30 was correlated with the decreasing of plasma FPG,2 hPG and TG(r=0.5812,0.6327,0.3872,P＜0.01),while HOMA-1R was related with the decreasing of plasma 2 hPG,TG and TC(r=0.8126,0.4671,0.2895,P＜ 0.01). HOMA-IR,△I30/△G30 and HOMA-β were lower (P＜0.01) and acarbose improved insulin resistance better (P＜0.05) in the elderly than in the younger with type 2 diabetes. Conclusions Pancreatic β-cell function declines gradually with aging,acarbose may have advantage over fenofibrate in improving early insulin secretion and resistance which was more relieved by diminishing glucotoxity in comparison with lipotoxity.
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The extraction method with organic solvent extraction to detect nitric oxide was improved, and the production of nitric oxide in mice myocardium in vitro was detected with this method. Using organic solvent (DETC)2-Fe2 + -NO complex was extracted from water phase into ester phase, and nitric oxide in sample of large volume can be detected by ESR at room temperature. The extracting ability of several organic solvents such as ethyl acetate, butyl acetate, glycerol triacetate, iso-amy lacetate, and n-butanol, was compared, and it was found that ethyl acetate was a good kind of organic solvent. There was a good linear relationship between the concentration of nitric oxide and ESR intensity within concentration of 20μmol/L, and the detected limit was improved to below 200 nmol/L; (DETC)2-Fe2+ -NO complex is easy to decompose in light but it is very stable in dark at 0～4℃ which, there is only a little change after ten days.