Trifluoromethanesulfonic acid,an alternative solvent medium for the direct electrophilic fluorination of DOPA: new syntheses of 6‐[18F]fluoro‐L‐DOPA and 6‐[18F]fluoro‐D‐DOPA

Previous work from this laboratory has shown that the direct fluorination of 3, 4‐dihydroxy‐phenyl‐L ‐alanine (L ‐DOPA) in anhydrous HF (aHF) or BF₃/HF with F₂ is an efficient method for the synthesis of 6‐fluoro‐L ‐DOPA. Since then, ¹⁸F‐labeled 6‐fluoro‐L ‐DOPA ([¹⁸F]6‐fluoro‐L ‐DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F₂ toward L ‐DOPA in CF₃SO₃H is comparable with that in aHF. This new synthetic procedure has led to the production of [¹⁸F]fluoro‐L ‐DOPA and [¹⁸F]fluoro‐D‐DOPA isomers in 17±2% radiochemical yields (decay corrected with respect to [¹⁸F]F₂). The 2‐ and 6‐FDOPA isomers were separated by HPLC and subsequently characterized by ¹⁹F NMR spectroscopy. The corresponding [¹⁸F]‐FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF. Copyright © 2007 John Wiley & Sons, Ltd.     

2型糖尿病患者T细胞亚群、TNF-α及IL-10的相关性研究

目的探讨2型糖尿病患者外周血T细胞亚群、血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-10之间的相关性.方法用流式细胞仪分析46例初诊2型糖尿病(DM组)患者和39例正常对照者(NC组)的外周血T细胞亚群水平,双抗夹心酶联免疫吸附法检测血清TNF-α、IL-10的水平.同时检测空腹血糖(FPG)、空腹胰岛素(FIns)、糖化血红蛋白(GHbA1c).结果DM组CD4 、CD4 /CD8份别为(48.89±5.50)%,2.64±0.57明显高于NC组的(34.52±3.04)%、1.52±0.27,差异均有统计学意义(P＜0.05);而CD8 则明显低于NC组[(20.16±1.65)%vs(28.28±3.27)%,P＜0.05];DM组和NC组的血清TNF-o水平[(12.71±5.37)ng/L vs(8.17±2.80)ng/L],差异有统计学意义(P＜0.05);而2组血清IL-10的水平差异无统计学意义[(4.61±1.20)ng/L vs(4.36±0.84)ng/L,P＞0.05].结论机体免疫功能异常与促炎因子的启动在2型糖尿病的发生、发展中发挥着一定的作用.     

白细胞介素-2对高糖状态下人视网膜色素上皮细胞的影响

目的研究白细胞介素-2(IL-2)对高糖状态下人视网膜色素上皮(RPE)细胞的增殖及其分泌和表达血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的影响。方法MTT自动比色法观察IL-2浓度对高糖状态下RPE细胞增殖的作用;ELISA法测RPE细胞分泌VEGF的变化;免疫组化观察RPE细胞表达VEGF的变化。结果0.1～10μg/L的IL-2均能明显促进高糖状态下RPE细胞的增殖,并能明显提高RPE细胞分泌VEGF的水平及提高VEGF在细胞中的表达。结论高糖状态下,IL-2可明显促进人RPE细胞的增殖并能提高RPE细胞分泌VEGF的水平和提高VEGF在RPE细胞中的表达,IL-2可能在增殖性糖尿病视网膜病变中起一定的作用。     

桂枝汤有效成分苯丙烯类化合物干预IL-1β刺激小鼠脑微血管内皮细胞释放PGE2的构效关系

前期研究发现,桂枝汤解热有效部位A(Fr.A)在很小剂量(3.8~7.6mg.kg-1,po)即显示了明显的解热活性,并可降低发热动物下丘脑PGE2含量[1],经LC/MS,GC/MS和化学分离确证,其含十余种苯丙烯类化合物,此类化合物为该部位的主要成分。由于Fr.A中除桂皮醛、桂皮醇、2-甲氧基桂皮醛、香豆     

泼尼松在微小病变型肾病综合征发病中的作用

目的：研究白细胞介素-8在微小病变型肾病综合征发病过程中的作用和泼尼松对其影响。方法：24只健康Wistar大鼠随机分成3组,每组8只。对照组经尾静脉注射生理盐水0.5mL,实验组经尾静脉注射阿霉素6.0mg/kg（用生理盐水溶解至0.5mL）,观察组经尾静脉注射阿霉素6.0mg/kg及泼尼松2mg/kg,用蒸馏水溶解为0.5mL,用灌胃器注入胃内,1次/d,至实验结束。分别于第8天、第14天取血测白细胞介素-8浓度,并于第14天处死动物,每组随机取两只大鼠的肾组织行光镜和电镜检查。结果：对照组、实验组和观察组血浆白细胞介素-8浓度第8天分别为（0.41±0.15）μg/L、（0.69±0.15）μg/L和（0.53±0.11）μg/L;第14天分别为（0.45±0.12）μg/L、（0.605±0.095）μg/L和（0.477＋0.050）μg/L;3组间差别均有统计学意义（F分别为5.456和3.923,P〈0.01）。实验组肾组织电镜下改变主要为上皮细胞足突融合,观察组电镜下病理改变轻于实验组。结论：泼尼松可以通过抑制白细胞介素-8的分泌减轻肾脏的病理损伤。     

IL-6与肥胖和胰岛素抵抗的关系

目的：探讨血清IL-6水平以及IL-6基因多态性与肥胖和胰岛素抵抗（IR）的关系。方法：选取肥胖2型糖尿病患者55例（肥胖组），非肥胖2型糖尿病患者49例（非肥胖组），健康对照50例（对照组），应用酶联免疫法检测血清中IL-6水平，并应用PCR-RFLP方法检测IL-6-174启动子区基因多态性。结果：肥胖组血清IL-6水平较非肥胖组及对照组明显增高．在糖尿病组中IL-6-174G等位基因携带者体质量指数（BMI）及IR均高于IL-6-174C等位基因携带者。结论：IL-6与BMI和IR有关，携带IL-6-174G等位基因者更易于发生IR。     

何首乌对小鼠腹腔巨噬细胞功能的影响

为了解何首乌对小鼠腹腔巨噬细胞功能的影响,采用微量浊度法测定小鼠腹腔巨噬细胞介导的细胞毒活性;采用小鼠胸腺细胞检测法测定小鼠腹腔巨噬细胞白细胞介素-1的分泌活性;采用姬姆萨染色法检测小鼠腹腔巨噬细胞的吞噬功能。结果表明,各药物实验组小鼠腹腔巨噬细胞介导的细胞毒作用及泌白细胞介素-1的分泌活性明显增强(P<0.01);各药物实验组小鼠腹腔巨噬细胞的吞噬功能明显增强(P<0.01),提示何首乌能促进小鼠腹腔巨噬细胞功能。     

Synthesis of a [18F]fluorobenzothiazole as potential amyloid imaging agent

This study describes the synthesis of a fluoroethylated derivative of [N‐methyl‐¹¹C]2‐(4′‐methylaminophenyl)‐6‐hydroxybenzothiazole ([¹¹C]6‐OH‐BTA‐1; Pittsburgh Compound B (PIB)), an already established amyloid imaging agent. The [¹¹C]methylamino group of [¹¹C]6‐OH‐BTA‐1 was formally replaced by a fluoroethyl group in a cold synthesis via N‐alkylation of N‐Boc‐2‐(4′‐aminophenyl)‐6‐(methoxyethoxymethoxy)benzothiazole with fluoroethyl tosylate. Subsequent deprotection gave the target compound 2‐[4′‐(2‐fluoroethyl)aminophenyl]‐6‐hydroxybenzothiazole (FBTA). In a radioligand competition assay on aggregated synthetic amyloid fibrils using N‐[³H‐methyl]6‐OH‐BTA‐1, 100 nM FBTA inhibited binding with 93 ± 1 and 83 ± 1% efficiency for Aβ_1–40 and Aβ_1–42, respectively. For the radiosynthesis a precursor carrying a tosylethyl moiety was prepared allowing the introduction of [¹⁸F]fluoride via nucleophilic substitution with [¹⁸F]tetra‐n‐butyl‐ammonium fluoride (TBAF). Subsequent removal of all protecting groups was performed in a one‐pot procedure followed by semi‐preparative HPLC, delivering the target compound [¹⁸F]FBTA in good radiochemical yield of 21% on average and radiochemical purity of ?98% at EOS. In vitro autoradiography on human postmortem AD brain tissue slices showed intense cortical binding of [¹⁸F]FBTA (1 nM), which was displaced in presence of 6‐OH‐BTA‐1 (1 µM). Brain up‐take was evaluated in wild‐type (wt) mice with microPET imaging. Based on these results, [¹⁸F]FBTA appears to be a suitable candidate tracer for amyloid imaging in humans. Copyright © 2008 John Wiley & Sons, Ltd.     

A simple and rapid automated radiosynthesis of [18F]fluoroacetate

Two fully automated synthetic procedures of [¹⁸F]fluoroacetate ([¹⁸F]FAC) have been developed using a modified commercial TRACERlab FX_FN synthesizer. One was a two‐step one‐pot procedure, consisting of nucleophilic [¹⁸F]fluorination of benzyl‐2‐bromoacetate as a precursor with no‐carrier‐added [¹⁸F]fluoride, hydrolysis within the same [¹⁸F]fluorination reaction vessel, and purification with/without high‐performance liquid chromatography (HPLC). The second procedure consisted of nucleophilic [¹⁸F]fluorination, hydrolysis on the column, and purification with SEP‐PAK cartridges instead of HPLC. The radiochemical purity of [¹⁸F]FAC was >95% by the two procedures. The second procedure was a simple, rapid, and fully automated synthesis of [¹⁸F]FAC with a high and reproducible radiochemical yield exceeding 60% (decay uncorrected) within the total synthesis time less than 20 min. The new, simple, and rapid on‐column hydrolysis procedure should be adaptable to the fully automated synthesis of [¹⁸F]FAC at a commercial fluoro‐deoxyglucose synthesis module. Copyright © 2008 John Wiley & Sons, Ltd.     

Radiosynthesis of [18F]PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

PBR111 (2‐(6‐chloro‐2‐(4‐(3‐fluoropropoxy)phenyl)imidazo[1,2‐a]pyridin‐3‐yl)‐N,N‐diethylacetamide) is a novel, reported, high‐affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine‐18 (half‐life: 109.8 min) using our Zymate‐XP robotic system. The process involves (A) a simple one‐step tosyloxy‐for‐fluorine nucleophilic aliphatic substitution (performed at 165°C for 5 min in DMSO using K[¹⁸F]F‐Kryptofix^®222 and 6.8–7.6 µmol of the corresponding tosylate as precursor for labelling) followed by (B) C‐18 PrepSep cartridge pre‐purification and (C) semi‐preparative HPLC purification on a Waters Symmetry^® C‐18. Up to 4.8 GBq (130 mCi) of [¹⁸F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/µmol (2–4 Ci/µmol) in 75–80 min (HPLC purification and SepPak^®‐based formulation included), starting from a 37.0 GBq (1.0 Ci) [¹⁸F]fluoride batch. Overall non‐decay‐corrected isolated yields were 8–13% (13–21% decay‐corrected). Copyright © 2008 John Wiley & Sons, Ltd.