18F-FDG和11C-PIB PET联合脑显像对阿尔茨海默病及 额颞痴呆的鉴别诊断价值初探

目的 初步探讨11C-PIB和18F-FDG联合脑显像在阿尔茨海默病（AD）及额颞痴呆（FTD）鉴别诊断中的 应用价值。方法 10例难以鉴别为AD或FTD的患者,行11C-PIB及18F-FDG PET联合脑显像。18例年龄匹配的健康 老年人为对照组,行18F-FDG PET脑显像。18F-FDG结果应用统计参数图（SPM）进行基于体素水平分析,行2个样本t 检验,P < 0.001认为有统计学意义。选取11C-PIB廓清及滞留情况对比明显的55~60 min图像进行视觉分析,PIB阳性 定义为双侧额叶、顶叶、枕叶、颞叶及皮质下结构PIB放射性滞留较白质为著,小脑PIB廓清。PIB阴性定义为大脑皮 层及皮质下结构、小脑无明显PIB滞留,仅在脑白质走行区少量放射性滞留。结果 18F-FDG与11C-PIB PET脑显像 示典型AD图像5例,双侧颞-顶联合皮质区、楔前叶及后扣带回大脑葡萄糖代谢减低,PIB阳性。典型FTD图像2例, 双侧额叶、前扣带回及双侧皮质下结构大脑葡萄糖代谢减低,PIB阴性。3例患者经18F-FDG脑显像仍难以鉴别,但 11C-PIB脑显像提示AD 2例,FTD 1例,并且经5~6个月随访证实。结论18F-FDG和11C-PIB联合脑显像能为AD及FTD 鉴别诊断提供双重的影像学依据,尤其是在大脑葡萄糖代谢减低脑区相互重叠时,11C-PIB显像有助于进一步鉴别。     

早期帕金森病患者的临床与18F-FDG PET影像学特征研究

目的探讨早期帕金森病患者临床特征与18F-FDG正电子发射计算机断层显像的影像学特征及其在帕金森病早期诊断中的价值。方法选择我院神经内科门诊和住院收治的Hoehn-Yahr分级Ⅰ～Ⅱ级早期帕金森患者18例,另设正常对照组,与PD组年龄匹配的对照者20例。所有患者静脉注射18F-FDG后进行正电子发射计算机脑断层显像,获得双侧纹状体、丘脑等部位葡萄糖代谢图像,采用目测法对脑各部位的葡萄糖代谢进行判断,应用PET专用软件计算各ROI的18F-FDG放射性核素值,以枕叶为基准,计算脑部各ROI与枕叶的18F-FDG代谢放射性核素值的比值,在此基础上计算脑部各两两比较的18F-FDG代谢比值。结果早期帕金森组：脑各部结构显示清晰,部分患者大脑皮层显示轻度脑萎缩;大脑皮层示踪剂分布相对均匀,左右对称;皮层下各神经核团显示结构完整,清晰对称;18例早期帕金森病患者18F-FDG正电子计算机断层显像有16例可见脑内有不同程度的放射性分布异常,占88.89%,非对称性纹状体放射性减低14例（77.78%）,其中5例为双侧减低,患者的双侧纹状体放射性计数进行半定量比较,发现运动障碍肢体对侧（脑病侧）纹状体尾状核/小脑比值为1.12&#177;0.31,另侧（脑健侧）1.38&#177;0.28,病侧与健侧脑相应区域相比下降,差异显著（t=2.64,P〈0.05）;壳核/小脑比值分别为1.22&#177;0.28和1.46&#177;0.22（t=2.86,P〈0.01）。结论PET显像有助于早期发现亚临床期PD患者纹状体功能改变,可提高早期PD诊断的准确性。PD患者18F-FDGPET显像显示尾状核与壳核团的不对称性代谢减低改变,利用局部ROI的半定量分析方法,能反映出纹状体功能,有助于临床上早期诊断帕金森病并更为客观地评估病情和病程。     

氟代脱氧葡萄糖在PET／CT致痫灶定位显像中的应用

目的探讨正电子药物18F氟代脱氧葡萄糖（18F-FDG）在正电子发射计算机（断层PET／CT）脑显像致痫灶定位中的应用。方法对32例癫痫患者行18F-FDG脑三维PET／CT显像,将其定位结果与头皮脑电图（EEG）、颅脑CT或MRI结果进行比较。结果PET／CT阳性检出率为90．6％（29／32）,其中低代谢灶27例,高代谢灶2例,正常3例;EEG阳性检出率为65．6％（21／32）,常规脑部CT或MRI阳性检出率为31．0％（10／32）。结论18F-FDG在PETJCT脑显像中对癫痫的定位诊断有较高的灵敏性和准确性。     

新型18F-脱氧葡萄糖注射液的制备与质量控制

目的 研究^18F-脱氧葡萄糖(^18F-FDG)注射液的制备和质量控制方法。方法应用小型回旋加速器,通过^18O(p,n)^18F核反应生产出^18F离子,由亲核取代反应制备^18F-FDG,并对所制备的^18F-FDG注射液进行质量控制。结果采用新型^18F-FDG化学合成方法后,放射化学产率可达72％,HPLC法测定的化学纯度大于99％,TLC测定放化纯度大于95％,^18F-FDG注射液的各项质量控制指标均符合《美国药典》的要求。结论 新型^18F脱氧葡萄糖注射液可应用于临床PET的检查。     

正电子发射断层显象对胰腺癌的诊断及其价值

胰腺癌在临床早期诊断中尚属难点,正电子发射断层显像(positron emission computed tomography,简称PET)对胰腺癌的诊断已受到重视和关注.目前用于胰腺癌PET诊断的正电子放射性药物为氟化脱氧葡萄糖(18F-FDG).18F-FDG PET显像能显示组织中的葡萄糖摄取和代谢,恶性肿瘤组织的葡萄糖代谢的特点是糖酵解增强和葡萄糖摄取增加.基于这个机制,18F-FDG PET显像用于恶性肿瘤的诊断,包括胰腺癌的诊断.业已研究表明胰腺癌细胞表面葡萄糖转运体增多,其中Glut1基因过度表达,而此与癌细胞糖酵解增强相关联[1].     

18F-FDG显像剂在肿瘤患者应用中的护理观察

目的 探讨肿瘤患者注射18F-脱氧葡萄糖(18F-FDG)显像剂的护理效果.方法 选择2015年2月至2016年9月于本院注射18F-FDG行正电子发射断层成像(PET/CT)检查的肿瘤患者128例作为此次研究对象,随机把患者分为2组,每组64例,对照组实施常规检查护理,观察组在常规检查护理基础上加强注射18F-FDG显像剂的护理,对比两组患者的护理效果.结果 对照组患者配合度为78.13％,观察组患者配合度为90.63％,观察组显著高于对照组(P＜0.05);观察组患者行PET/CT检查的舒适度显著优于对照组(P＜0.05).结论 加强肿瘤患者行PET/CT检查注射18F-FDG显像剂的护理能够获得满意的护理效果,能够让患者在各方面均保持愉悦、舒适的状态,以此提高对检查的配合,改善PET/CT图像质量,值得推广.     

结合CT影像的正电子发射体层显像用于胸部肿瘤诊断

正电子发射体层显像（positron emission tomography，PET）在评价胸部肿瘤中的作用日益加强，目前认为是区分胸部肿瘤良恶性的最好方法。然而^18F-脱氧葡萄糖（^18F fluomdeoxyglucose，^18F-FDG）并非肿瘤特异性显像剂，PET显像不可避免地出现假阳性和假阴性，如何减少假阳性和假阴性一直是PET研究的热点。如能在阅读PET影像资料时结合CT图像（如诊断肺部病变结合病变的大小、位置、边缘、密度、有无钙化、脂肪成分、空洞、支气管充气征、增强后的密度改变等），则能大大降低假阳性和假阴性发生率。目前结合的方法有三种：分别阅读PET和CT影像资料；在计算机上利用融合软件处理PET和CT影像资料；用PET-CT一体机（integrated PET-CT）同时做PET和CT检查。[第一段]     

18F-FDG PET/CT显像联合HRCT对孤立性肺结节的应用价值

目的 应用18 F-FDG PET/CT代谢显像联合HRCT对孤立性肺结节(SPN)的诊断价值.方法 回顾性分析2017年6月至2018年12月经术后病理证实及临床随访2年的孤立性肺结节患者50例,汇总其影像及临床检查等资料.结果 50例患者中,确诊肺癌43例,良性7例.单行18 F-FDG PET/CT显像检查的病例...     

耳鸣患者PET显像的相关脑区探讨

目的：探讨耳鸣患者脑PET18 F-FDG代谢的相关脑区。方法通过对41例耳鸣患者及40例健康对照组进行PET-CT检查,行踪剂为18 F-FDG,结果用统计参数图(SPM)软件进行统计分析,确定与耳鸣相关脑区的解剖部位(BA)。结果耳鸣患者相关脑区主要位于左侧颞下回(BA20)、左侧颞中回(BA21)、左侧颞上回(BA22)、左侧腹侧后扣带皮层(BA24)、左侧颞极区(BA38)及右侧后外侧前额叶皮层(BA9)、右侧额极区(BA10)、右侧眶额回(BA11)、右侧颞下回(BA20)、右侧背侧前扣带皮层(BA32)、右侧海马旁皮层(BA36)、右侧梭状回(BA37)。结论耳鸣患者在中枢神经系统可能存在特定的投射区,主要位于边缘系统及额叶联合区,与主次级听觉皮层有一定关系。PET 为耳鸣提供了客观证据,有望成为耳鸣的客观检测方法。     

多巴胺D2受体显像剂^131I—epidepride的临床研究

目的：研究多巴胺D2受体显像剂epidepride在动物体内，脑内动态分布规律及显像特点，为进一步临床应用提供依据。方法：采用双氧水法标记制得^131I-epidepride。取SD大鼠，注射^131I-epidepride考察其大鼠体内，脑内结合分布特点，家兔2只用于SPECT显像，一只兔于注射后连续采集，应用ROI技术，获得相应时间－放射性曲线，另一只兔据结果选用epidepride在脑内分布最高时期，行脑断层显像，结果：双氧水法标记率大于95％，体内心肺吸收迅速，清除最快，该药从肝胆及胃肠系统代谢，脑内纹状体浓聚稳定，小脑清除快，显像研究示纹状体有较高浓集，结论：应用双氧水法标记epidepride,标记率高。^131I-epidepride在纹状体内有高度稳定浓集，是一种良好，有效的多巴胺D2受体显像剂。     

腹腔注射L-丝氨酸后大鼠梗死侧脑皮质L-丝氨酸与D-丝氨酸含量的测定

目的:制作大鼠永久性脑梗死模型,腹腔注射L-丝氨酸,测定梗死侧大脑皮质L-丝氨酸与D-丝氨酸含量的变化,为应用L-丝氨酸辅助治疗脑梗死提供方法学上的依据。方法:利用邻苯二甲醛及N-乙酰半胱氨酸柱前衍生,高效液相色谱荧光检测法测定脑组织中L-丝氨酸与D-丝氨酸含量。结果:流动相A为82%0.1 mol·L-1磷酸盐缓冲液,流动相B为18%甲醇条件下,L-丝氨酸与D-丝氨酸得到很好的分离;腹腔注射L-丝氨酸1 h后,梗死侧脑皮质L-丝氨酸含量迅速增加,2 h即达高峰[(6.85±0.30)μmol·g-1],为正常脑组织的4倍以上,12 h时仍是正常的2倍以上水平[(3.56±0.22)vs(1.52±0.04)μmol·g-1];D-丝氨酸水平升高缓慢,升高幅度低,6 h时达高峰,为正常的2倍多[(0.75±0.05)vs(0.32±0.01)μmol·g-1]。结论:腹腔注射L-丝氨酸能快速升高梗死侧大脑皮质L-丝氨酸水平,对D-丝氨酸影响相对较小。     

18F-氟代脱氧葡萄糖诱导MCF-7细胞株的凋亡研究

目的研究18F-氟代脱氧葡萄糖(18F-FDG)诱导体外培养MCF-7乳腺癌细胞的凋亡情况。方法不同剂量18F-FDG加入体外培养MCF-7乳腺癌细胞中共培养,以γ计数仪测定细胞摄取18F-FDG的量;用流式细胞仪测定细胞早期和晚期凋亡率;用TUNEL法测定细胞凋亡的数量。结果①相同数量级的MCF-7细胞对18F-FDG的摄取量与剂量增加呈线性;②流式细胞结果示:经12 h18F-FDG孵育引起MCF-7的平均早期凋亡率为12.5%,平均晚期凋亡率为39.3%,总平均凋亡率为51.8%。经24 h18F-FDG孵育引起MCF-7的平均早期凋亡率为10.4%,平均晚期凋亡率为42.1%,总平均凋亡率为52.5%;③TUNEL显示:用凋亡指数(apoptotic index,AI)表示,与空白对照组AI(5.13±1.51)%相比,18F-FDG孵育12 h爬片的AI为(45.93±1.51)%,18F-FDG孵育24 h爬片的AI为(46.93±1.52)%。结论一定剂量范围内,18F-FDG对MCF-7细胞诱导凋亡效果显著。     

Review. 18F-FDG PET in the diagnosis and follow-up of thyroid malignancy

The diagnosis of carcinoma of the thyroid is usually made in the process of investigating a thyroid nodule with clinical examination, Technetium-99m scan, ultrasonography and fine-needle aspiration (FNA) cytology. The follow-up is mainly based on 123-iodine and 131-iodine scans and serum thyroglogulin measurement. The aim of the present review was to establish the role of 18F-FDG PET in the differential diagnosis of doubtful thyroid nodules and in the follow-up of patients with increased serum thyroglobulin levels and negative iodine-scan. It remains to be defined if metabolic imaging with PET could be a useful routine procedure in the management of thyroid tumours since the majority of them are well-differentiated and therefore have less avidity to 18F-FDG. In the present work we collected the specific literature derived from MEDLINE over the last 10 years to clarify the potential clinical value of 18F-FDG PET in thyroid malignancies. An emerging role for 18F-FDG PET is in the assessment of incidental finding of a thyroid nodule which, when showing high FDG uptake should be regarded as a possible malignancy that needs further assessment. Another well-documented role for 18F-FDG PET is in the investigation of cases of established well-differentiated thyroid carcinomas presenting with high thyroglobulin and negative iodine imaging. An increase of the 18F-FDG uptake in these tumours indicates a shift towards lesser differentiation (with more aggression and poor prognosis) and may benefit from alternative management. 18F-FDG PET can be considered a routine functional imaging method in detecting iodine-negative recurrent disease in thyroid cancer patients with elevated serum thyroglobulin levels during follow-up. 18F-FDG PET seems to be useful also in differential diagnosis of suspected thyroid nodules, especially using the semi-quantitative SUV analysis.     

利用Siemens Explora FDG4化学合成模块合成18F-FDG的方法及质量控制

目的:建立18F-FDG注射剂的合成工艺及质量控制方法.方法:采用西门子公司的Explora FDG4化学合成模块合成可供注射用的18F-FDG.结果:制得18F-FDG注射剂,TLC测定放射化学纯度大于98%,合成效率达58%以上.结论:采用本方法合成18F-FDG注射剂可在满足日常检查需要的同时最大限度的减少工作人员受到的辐射.     

Alterations of neuroimmune cell density and pro-inflammatory cytokines in response to thimerosal in prefrontal lobe of male rats

Evidence suggests that the effect of heavy metals on neuroimmune cells lead to neurogenic inflammatory responses. In this study, immune cells [mast cells (MCs) and microglia] and pro-neuroinflammation cytokines (interleukin-1b and tumor necrosis factor-α) were assessed in the prefrontal lobe of rat brains exposed to thimerosal in different timeframes. A total of 108 neonatal Wistar rats were divided into three groups having three subgroups. The experimental groups received a single dose of thimerosal (300?μg/kg) postnatally at 7, 9, 11, and 15?days. The vehicle groups received similar injections of phosphate-buffered saline in a similar manner. The control groups received nothing. Samples of the prefrontal cortex were collected and prepared for stereological, immunohistochemical, and molecular studies at timeframes of 12 or 48?h (acute phase) and 8?days (subchronic phase) after the last injection. The average density of the microglia and MCs increased significantly in the experimental groups. This increase was more evident in the 48?h group. At 8?days after the last injection, there was a significant decrease in the density of the MCs compared to the 12 and 48?h groups. Alterations in pro-inflammatory cytokines were significant for all timeframes. This increase was more evident in the 48?h group after the last injection. There was a significant decrease in both neuroinflammatory cytokines at 8?days after the last injection. It was found that ethylmercury caused abnormal neurogenic inflammatory reactions and alterations in the neuroimmune cells that remained for a longer period in the brain than in the blood.     

Lonomia obliqua caterpillar venom increases permeability of the blood-brain barrier in rats.

Human envenoming by caterpillars of the saturniid moth Lonomia obliqua in southern Brazil produces a mild local response (erythema, some edema, and pain) and systemic effects that include incoagulable blood, renal failure and in severe accidents intracerebral hemorrhage. In this work, we used light and electron microscopy to investigate the morphological alterations in the brain and blood-brain barrier of rats injected intravenously with venom from L. obliqua spicules (200 microg/kg). Five semi-purified fractions of venom (200 microg/kg each) were also assayed. Quantitative morphological and ultrastructural analyses were done 6, 18, 24 and 72 h after the i.v. injection of venom and its fractions. Light microscopy showed that 6h after envenoming there was cerebellar edema, which decreased by 72 h. Intracerebral hemorrhage occurred in only one rat 24h after the injection of venom. Blood-brain barrier (BBB) breakdown, assessed by transmission electron microscopy based on the passage of an extracellular tracer (lanthanum nitrate) between brain capillary endothelial cells, was observed in the cerebellum and hippocampus 18 h after venom injection. At this time, the cerebellum was more sensitive to the venom than the hippocampus, as shown by the greater number of leaky vessels. The number of capillaries showing breakdown was lower after 72 h than after 18 h. None of the semi-purified fractions significantly increased the number of leaky vessels. These results indicate that L. obliqua caterpillar venom has a deleterious action on the rat BBB. The lack of effect of the venom fractions when administered alone suggested that a synergistic action of venom components may be responsible for the damage seen in the central nervous system, but this was not confirmed when three combinations of the fractions were tested.     

Influence of P-Glycoprotein Inhibition or Deficiency at the Blood–Brain Barrier on 18F-2-Fluoro-2-Deoxy-d-glucose (18F-FDG) Brain Kinetics

The fluorinated d-glucose analog ¹⁸F-2-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein’s (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact ¹⁸F-FDG incorporation, suggesting that P-gp function at the blood–brain barrier may also modulate ¹⁸F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of ¹⁸F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for ¹⁸F-FDG brain kinetics were then assessed using (i) ¹⁸F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg⁻¹ h⁻¹) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled d-glucose exposure to the brain. In vitro, the time course of ¹⁸F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of d-glucose but not in the presence of high d-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K₁, k₂, k₃, V_T, and CMR_Glc. The lack of P-gp effect on in vivo¹⁸F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates ¹⁸F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. ¹⁸F-FDG is not a P-gp substrate at the BBB and ¹⁸F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.KEY WORDS: ABC transporters, blood–brain barrier, cyclosporine, glucose, multidrug resistance, nonhuman primate, positron emission tomography     

Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats.

Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin were prepared as drug delivery systems. The pharmacokinetics and tissue distribution of doxorubicin in these SLN were studied after i.v. administration to conscious rats and were compared to the commercial solution of doxorubicin. The same dose of each formulation (6 mg kg(-1)of body weight) of doxorubicin was injected in the rat jugular vein. Blood samples were collected after 1, 15, 30, 45, 60 min and 2, 3, 6, 12, and 24 h after the injection. Rats were sacrificed after intervals of 30 min, 4 h, and 24 h and samples of liver, spleen, heart, lung, kidney, and brain were collected. In all samples, the concentration of doxorubicin and of the metabolite, doxorubicinol, were determined. Doxorubicin and doxorubicinol were still present in the blood 24 h after injection of stealth and non-stealth SLN, while they were not detectable after the injection of the commercial solution. The results confirmed the prolonged circulation time of the SLN compared to the doxorubicin solution. In all rat tissues, except the brain, the amount of doxorubicin was always lower after the injection of the two types of SLN than after the injection of the commercial solution. In particular, SLN significantly decreased the heart concentration of doxorubicin.