New radiolabelling chemistry: synthesis of phosphorus–[18F]fluorine compounds

The feasibility of synthesizing compounds containing the P–¹⁸F bond has been demonstrated by labelling the pesticide, cholinesterase inhibitor Dimefox (N,N,N′N′‐tetramethylphosphorodiamidic fluoride) with F‐18. Radiolabelling was achieved in high radiochemical yield (96%) by nucleophilic substitution of the chloro group attached to phosphorus, in the oxidation state P(V), by ¹⁸F^? (activated with tetrabutylammonium carbonate in acetonitrile). Given the large number of important biological molecules possessing phosphorus such as oligonucleotides, phospholipids as well as phosphorylated proteins, sugars and steroids, this new labelling chemistry may provide an additional route to radiolabelling these biologically important compounds for use in PET. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of 2‐[(2‐chloro‐2′‐[18F]fluoroethyl)amino]‐2H‐1,3,2‐oxazaphosphorinane‐2‐oxide (18F‐fluorocyclophosphamide), a potential tracer for breast tumor prognostic imaging with PET

A fluorine‐18 labeled analog of the widely used chemotherapeutic agent cyclophosphamide was synthesized as a tracer for prognostic imaging with positron emission tomography. 2‐[(2‐Chloro‐2′‐[¹⁸F]fluoroethyl)amino]‐2H‐1,3,2‐oxazaphosphorinane‐2‐oxide (¹⁸F‐fluorocyclophosphamide), was prepared by direct halogen exchange reaction from the parent cyclophosphamide. In small‐scale syntheses, radiochemical yields of up to 4.9% and specific activities of 960 Ci/mmol were achieved in a total synthesis time of 60–75 min. The [¹⁸F]‐labeled cyclophosphamide analog with radioactive purity >99% and chemical purity >96% was suitable for in vivo (microPET imaging) and ex vivo studies of a murine model of human breast tumors. Copyright © 2005 John Wiley & Sons, Ltd.     

稽留流产患者血清和绒毛组织E_2、P、β-hCG、IL-18、PDCD-5的表达及其预警意义

目的:探讨E_2、P、β-hCG、IL-18、PDCD-5在稽留流产患者血清和绒毛组织的表达及其预警意义。方法:选取2018年1—6月我院收治稽留流产妇女30例作为实验组,同期就诊正常早孕妇女(要求终止妊娠)30例为对照组,测定患者血清和绒毛组织E_2、P、β-hCG、IL-18、PDCD-5表达水平,通过统计学软件分析这些指标与孕妇发生稽留流产的相关性。结果:与对照组相比,实验组受试者血清、绒毛组织中E_2、P和β-hCG水平明显较低(P<0. 05),IL-18和PDCD-5水平明显较高(P<0. 05)。Logistic多元回归分析结果显示,血清E_2、P、β-hCG低表达以及IL-18、PDCD-5高表达为孕妇发生稽留流产的危险因素(P<0. 05)。结论:血清、绒毛组织中E_2、P、β-hCG低表达以及IL-18、PDCD-5高表达与孕妇稽留流产发生有关,具有一定预警作用。     

18F-FDG PET/CT在探查腹膜转移性肿瘤中的价值

目的:评价18F-FDG PET/CT探查腹膜转移瘤的价值。方法:39例有腹部原发恶性肿瘤手术史患者行PET/CT首次和延迟扫描,在PET/CT图像上记录病灶大小、分布,结果与常规CT比较。测量62个病灶和对照组32例腹部无病变患者的肠管SUVmax。所有病例经手术、病理、影像学和肿瘤标记物随访作出最后诊断。结果:最终确认39例中31例腹膜转移瘤,病灶均为结节状或沿腹膜条片状分布,多位于肝脏周围和盆腔腹膜,其他部位腹膜少见。PET/CT漏诊的4个病灶主要位于肝脏周围,1例因化疗不久病灶FDG低摄取而漏诊,因此敏感性为87.1%,特异性为87.1%。CT仅检出12例转移瘤。转移瘤SUVmax明显高于对照组肠管SUVmax(P=0.0000)。结论:18F-FDG PET/CT能够较CT更早、更多地检出腹膜转移瘤,病灶体积小、位于基础摄取较高的肝脏周围是漏诊主要原因,而结合原发肿瘤病史和肿瘤标记物检查有利于诊断。     

Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation

Aims: Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. Methods: We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using¹⁸fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day,n=16) for 12weeks.¹⁸F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function. Results: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%).¹⁸F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of¹⁸F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery. Conclusions: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.     

胸痹心痛与血清IL-6、IL-1O、IL-18水平关系的研究

目的 研究胸痹心痛(冠心病心绞痛)发病与血清IL—6、IL—10、IL—18水平变化的关系。方法 观察胸痹心痛患者血清IL—6、IL—10、IL—18的水平并与健康人对比。结果 与稳定型心绞痛患者血清IL—10水平相比，不稳定型心绞痛患者血清IL—10水平较低，而IL—6水平较高；胸痹心痛患者IL—18水平均高于对照组。结论 血清IL—6、IL—10、IL—18水平的变化与胸痹心痛的发病密切相关。     

18β-甘草次酸对HO-8910PM细胞Fas/FasL表达的影响

目的研究18β-甘草次酸(18β-glycyrrhetinic acid,18β-GA)对人高转移卵巢癌HO-8910PM细胞中Fas,FasL表达的影响,探讨Fas,FasL对卵巢癌细胞凋亡的作用机制。方法不同浓度药物作用HO-8910PM细胞,MTT法检测细胞的生长增殖,流式细胞仪检测细胞周期,FITC法检测Fas,FasL的蛋白表达情况。结果 18β-GA对高转移卵巢癌细胞HO-8910PM的生长和增殖具有显著的抑制作用;药物使8910PM细胞周期阻滞于G1期,凋亡增加。FITC检测发现Fas,FasL蛋白表达上调(P<0.05)。结论 18β-GA通过上调HO-8910PM中Fas,FasL蛋白表达,促使细胞凋亡,抑制细胞增殖,提示18β-GA可能成为治疗卵巢癌的潜在药物。     

谷参肠安对溃疡性结肠炎患者细胞因子的影响

目的:探讨谷参肠安胶囊(L-谷氨酰胺、甘草、茯苓和白术)治疗活动期溃疡性结肠炎(UC)的疗效及对细胞因子的影响。方法:活动期UC患者82例,随机分为两组,对照组(39例)口服柳氮磺胺吡啶(或美沙拉嗪),同时用琥珀酸氢化考的松及庆大霉素、蒙脱石散保留灌肠,治疗组(43例)在上述治疗基础上,口服谷参肠安胶囊。治疗2个月后评价两组疗效以及患者血中细胞因子IL-10和IL-18的变化。结果:治疗后两组临床表现总评分明显下降,且治疗组优于对照组,两组比较差异有统计学意义(P0.05)。两组治疗后结肠镜表现均有改善,治疗组优于对照组;疾病活动指数(DAI)降低(P0.05),降低幅度治疗组优于对照组(P0.05)。两组均未见明显的不良反应。治疗后细胞因子IL-10的水平升高,且治疗组优于对照组,而IL-18虽有降低,但两组间无统计学差异。结论:谷参肠安口服辅助治疗活动期UC近期疗效明显。     

白细胞介素-18基因rs1946518位点多态性与肠道病毒71型感染易感性的关系

目的 探讨白细胞介素(interleukin,IL)-18基因rs1946518位点多态性与肠道病毒71型(enterovirus 71,EV71)感染易感性及其与EV71感染致病严重程度之间的相关性.方法 选取2012年3月至2014年12月湖南省湘潭市中心医院确诊的EV71感染患儿123例作为研究对象(EV71感染组),匹配同期在我院健康体检的52例儿童作为对照组.其中EV71感染组分为轻症EV71感染组(简称轻症组,n=62)和重症EV71感染组(简称重症组,n=61),提取DNA后通过测序分析IL-18基因rs1946518位点多态性.结果 EV71感染组与对照组均存在rs1946518位点多态性,EV71感染组AA、AC、CC基因频率分别为27.64%、50.41%、21.95%,A等位基因及C等位基因的频率分别为52.85%、47.15%,对照组AA、AC、CC的基因频率分别为26.92%、42.31%、30.77%,A等位基因及C等位基因的频率分别为48.07%、51.93%,EV71感染组与对照组基因型及等位基因频率经统计学分析,差异无统计学意义(P<0.05).轻症组AA、AC、CC的基因频率分别为14.51%、54.84%、30.65%,A等位基因及C等位基因的频率分别为41.94%、58.06%;重症组AA、AC、CC的基因频率分别为40.98%、45.90%、13.12%.A等位基因及C等位基因的频率分别为63.93%、36.07%,轻症组与重症组基因型分布频率差异具有统计学意义(χ2=12.58,P=0.002).轻症组与重症组等位基因频率差异亦具有统计学意义(χ2=11.94,P=0.001,OR=2.455,95%CI 1.496-4.102).结论 IL-18 rs1946518A/C位点基因多态性与EV71感染严重程度之间有一定程度的相关性,携带IL-18 rs1946518A等位基因的感染患儿进展为重症的概率较高.