[P-CH_3-~3H]-梭曼的合成

本文合成了〔P-CH_3-~3H〕-1,2,2-三甲基丙氧基甲膦酰氟(〔=P-CH_3-~3H〕-梭曼).放射比度1.4ci/mmol,放射化学纯度95%以上.     

[~3H]-乙酰紫草素在小鼠体内的组织分布、排泄及血中分布研究

目的:用氧化燃烧炉样品预处理技术研究[3H]-乙酰紫草素在小鼠体内的组织分布、排泄和血中分布.方法:小鼠单次灌服[3H]-乙酰紫草素后,收集组织、血、尿和粪样,氧化燃烧炉法进行样品预处理,液闪计数仪测定放射性水平.结果:小鼠单次灌胃给[3H]-乙酰紫草素(120 mg/kg,2.96×107 Bq/kg)后,放射性主要分布在胃、肠,其次是胆囊、肝、肾、肺,脑和脊髓分布较少.271 h后从粪中收集到给药剂量的(68.5 ± 3.3)%,尿中收集到(17.6± 3.1)%,粪尿合计(86.1 ± 5.5)%.另对乙酰紫草素在血中存在形式、血细胞和血浆中的分配比例以及与血浆蛋白结合的形式、结合率进行了探索性研究.结论:乙酰紫草素吸收较差;组织分布广泛;排泄较完全;1 h血样中没有检测到原形;血浆、血细胞药物含量分配比约为4∶ 1;人血浆蛋白结合率高;血浆蛋白的结合为共价和疏水作用两种形式并存.     

双氢埃托啡舌下含片的手术后镇痛效果

双氢埃托啡(DHE)是东罂粟碱类高效镇痛剂之一。本文观察了DHE舌下含片对129例术后患者的镇痛效果。DHE在不同剂量的镇痛有效率:20μg为80％,40μg为95％,50μg为100％。7例患者无效。20、40和50μg剂量生效时间分别为14、16和16min,持续有效时间分别为173、221和262min。40～80μg有7例产生副作用,出现呼吸减慢(11次/min)、头晕、恶心、呕吐,其中1例还出现面色苍白、出汗、血压下降。这些副作用在稍加休息后均可恢复。观察结果表明,DHE舌下含片顿服30～40μg对手术后患者是适用的。     

[3H]西达本胺在大鼠体内的排泄研究

目的:运用氧化燃烧炉预处理样品技术对[3H]西达本胺在大鼠体内的排泄进行研究;并运用同位素标记技术初步推断西达本胺在大鼠体内的代谢产物。方法:采用氧化燃烧炉处理[3H]西达本胺粪、尿、胆汁样品,用液闪计数仪测定其放射性水平。结果:方法学确证研究结果显示粪、尿、胆汁样品3H回收率基本为100%,精密度和准确度均小于10%。大鼠单次灌胃给[3H]西达本胺(1.2 mg/kg,1.24 mC i/kg),336 h后从粪中收集到给药剂量的(63.28±12.40)%,尿中收集到(18.77±3.21)%,粪尿合计(82.25±13.15)%;给药后48 h胆汁排泄出给药剂量的(4.28±2.72)%。另外,经HPLC仪收集纯化样品后测定放射性得到的色谱图发现在大鼠血浆、粪、尿和胆汁中均有西达本胺代谢物峰,原形药物在图谱上的放射性约占50%。结论:氧化燃烧法用于处理[3H]西达本胺的大鼠粪、尿、胆汁样品简便、准确。大鼠灌服给药后,在血浆、粪、尿和胆汁中均发现有西达本胺原形药物和代谢产物,约有一半以原形排出体外。     

琥珀酰亚胺[2,3-~3H]丙酸酯对乙酰胆碱酯酶的标记

琥珀酰亚胺[2,3-~3H]丙酸酯是一种有效的酰化试剂,可以标记乙酰胆碱酯酶并且保留较高的酶活性。它也适用于其它蛋白质、多肽和伯胺化合物的标记。此试剂已在我所合成,现在可以得到。     

心肌显像剂[99Tcm(CO)3(MIBI)3]+和99Tcm-MIBI药理实验对比研究

目的对心肌显像剂羰基99Tcm-甲氧基异丁基异腈(MIBI)([99Tcm(CO)3(MIBI)3]+)和99Tcm-MIBI进行动物药理对比研究.方法制备[99Tcm(CO)3(MIBI)3]+注射液,放化纯85%.实验犬3只,每次静脉注射剂量555 MBq,通过动态采集、全身显像和采集血样,获得药代动力学参数、体内生物分布、靶/非靶比值和药效学结果.结果 [99Tcm(CO)3(MIBI)3]+符合一次静脉给药的药代动力学二室模型,快相清除半衰期T(α)1/2=(1.33±0.12) min,慢相清除半衰期T(β)1/2=(102.33±25.58) min,总清除速率(CL)=(401.33±73.51) mL/h.心、肝、肺时间-放射性曲线显示[99Tcm(CO)3(MIBI)3]+肝摄取曲线幅度低于心肌曲线,而99Tcm-MIBI肝曲线明显高于心肌曲线.10、30、60、90和120 min[99Tcm-(CO)3(MIBI)3]+在心、肺、肝百分注射剂量(%ID)与99Tcm-MIBI比较,前者心肌摄取较高,肺本底较低,肝摄取低.[99Tcm(CO)3(MIBI)3]+心/肺和心/肝比值均高于99Tcm-MIBI,差异有显著性,P均<0.01.静脉注射[99Tcm(CO)3(MIBI)3]+后10～120 min均可获得清晰的心肌图像,肝胆排泄较快,肝内放射性较低,左室下壁不受肝影影响,无需脂餐促进肝胆排泄.结论 [99Tcm(CO)3(MIBI)3]+有望成为一种新的心肌灌注显像剂.     

~(131)Ⅰ-HpD在小鼠体内的吸收、分布和排泄

血卟啉衍生物（即HpD，定位标记为131I-HpD），经小鼠尾静脉注射后，血药浓度下降较快，全身分布迅速广泛，24至32小时变化较为平缓，32小时后几无变化。肺、脾、肝分布较多，肌肉最少，其它组织介于中间，8小时后血液、甲状腺、肺、肝、大腿肌肉等组织呈下降趋势，而肿瘤组织分布相对较多。与其它组织（肺肝除外）相比，具有相对选择性吸收和潴留作用，这种作用在24小时后较为明显。该药72小时内粪排量（57．5％）大于尿排量（42．5％）。血中放射性一时间曲线符合开放二室模型。     

13N-NH3·H2O动物体内分布及临床应用

目的研究13N-NH3·H2O的临床前药理、PET显像方法及其在心肌显像中的应用.方法进行犬全身和动态心肌PET显像,测定13N-NH3·H2O在犬体内的分布,并对健康志愿者进行心肌PET显像.结果心肌PET显像发现,心脏和肺是首过器官,心肌摄取率最高.心肌摄取快而清除相对较慢,血、肝和肺的本底清除快,心脏影像清晰.注射13N-NH3·H2O后30 s,左右心室放射性达到峰值,1 min后开始下降,在4～20 min保持相对平稳的水平;左心室间壁和侧壁心肌在注射后10 s开始摄取,间壁摄取高于侧壁,2 min后侧壁摄取略高于间壁;肝和肺在第30 s摄取达峰值,此后急剧下降,5 min后摄取逐渐下降并维持在较低的水平,心/肝和心/肺比值均高于2.0.动物全身显像发现,13N-NH3·H2O主要分布在血液供应丰富的组织,主要经肾脏清除.动态心肌显像和注射13N-NH3·H2O 4～5 min后进行的静态显像可获得一致的心肌血流灌注图像.结论 13N-NH3*H2O有较高的心/肝和心/肺比值,灌注图像清晰,是理想的心肌血流灌注显像剂.     

苯并[d]噻唑啉-2-酮-6-甲酸的合成研究

目的 设计一条简便、高效的合成路线用于苯并[d]噻唑啉-2-酮-6-甲酸的合成.方法 对氨基苯甲腈经硫氰化、关环、水解制得4-氨基-3-巯基-苯甲酸,再与氯甲酸乙酯环合反应得到苯并[d]噻唑啉-2-酮-6-甲酸.结果 目标化合物经1H-NMR和MS确证,新设计路线的总收率约62.2%.结论 本研究采用价廉易得的对氨基苯...     

牛小脑γ-氨基丁酸受体的溶液化及其纯化

牛小脑突触膜GABA受体经非离子型去垢剂(Nonidet P40)溶液化和超滤分离后于4℃冰箱或0℃放置5天左右,其[~3H]-GABA特异结合活性(cpm/mg蛋白)较膜结合GABA受体提高115倍,该结合活性至少可维持20天。根据该蛋白与[~3H]-GABA特异结合的可饱和性、可逆性、高亲和部位的存在及其配基专一性等,表明它仍具备膜结合GABA受体的特征。该受体蛋白不具有[~3H]-氟硝基安定的结合活性,在7.5%聚丙烯酰胺凝胶电泳为单一染色区带,等电点5.2左右,SDS聚丙烯酰胺凝胶电泳显示两种亚基,主要亚基为4.4万道尔顿。对该受体蛋白的理化性质及分子量大小进行了初步观察。     

Alzheimer病的~1H MRS初步探讨

目的 :探讨质子磁共振波谱分析(1HMRS)在Alzheimer病(简称AD)诊断中的作用。材料和方法 :32名ProAD患者分为两组 ,重度AD组11名 ,轻度AD组21名 ,与24名年龄相当的健康自愿者进行对照研究。采用PRESS序列 ,2cm×2cm×2cm大小体素定位于跨中线枕叶皮质区。分别计算各代谢物信号强度与肌酸的比值 ,并比较各组间的差别。结果 :重度AD组的NAA/Cr比值较轻度AD组和正常对照组均明显降低(p<0.05) ,而轻度AD组和对照组之间的差异无统计学意义。三组间的Cho/Cr比值无差异。结论 :AD患者枕叶NAA/Cr比值的降低反映了神经元的退变、萎缩。1HMRS为疾病监测提供了辅助信息。     

Differential uptake of [18F]FET and [3H]l-methionine in focal cortical ischemia

Amino acids such as [(11)C-methyl]l-methionine are particularly useful in brain tumor diagnosis, but unspecific uptake (e.g., in cerebral ischemia) has been reported. O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) shows a clinical potential similar to that of l-methionine (MET) in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of [(18)F]FET and [(3)H]MET in focal cortical ischemia in rats by dual-tracer autoradiography. METHODS: Focal cortical ischemia was induced in 25 CDF rats using the photothrombosis (PT) model. At different time points up to 6 weeks after the induction of PT, [(18)F]FET and [(3)H]MET were injected intravenously. Additionally, contrast-enhanced magnetic resonance imaging (MRI) was performed in 10 animals. One hour after tracer injection, brains were cut in coronal sections and evaluated by dual-tracer autoradiography. Lesion-to-brain (L/B) ratios were calculated by dividing the maximal uptake in the lesion by the mean uptake in the brain. An L/B ratio of >2.0 was considered indicative of pathological uptake. Histological slices were stained by cresyl violet and supplemented by immunostainings for glial fibrillary acidic protein (GFAP) and CD68 in selected cases. RESULTS: A variably increased uptake of both tracers was observed in the PT lesion and its demarcation zone up to 7 days after PT for [(18)F]FET and up to 6 weeks for [(3)H]MET. The cutoff level of 2.0 was exceeded in 12/25 animals for [(18)F]FET and in 18/25 animals for [(3)H]MET. Focally increased tracer uptake matched contrast enhancement in MRI in 3/10 cases for [(18)F]FET and in 5/10 cases for [(3)H]MET. Immunohistochemical staining in lesions with differential uptake of [(18)F]FET and [(3)H]MET revealed that selective uptake of [(18)F]FET was associated with GFAP-positive astrogliosis while selective [(3)H]MET uptake correlated with CD68-positive macrophage infiltration. CONCLUSIONS: [(18)F]FET, like [(3)H]MET, may exhibit significant uptake in the periphery of cortical infarctions, which has to be considered in the differential diagnosis of unknown brain lesions. There are discrepancies between [(18)F]FET and [(3)H]MET uptake in the area of infarctions that appear to be caused by the preferential uptake of [(18)F]FET in reactive astrocytes versus the preferential uptake of [(3)H]MET in macrophages.     

Simplified PET measurement for evaluating histamine H1 receptors in human brains using [11C]doxepin

The aim of this study was to develop simplified positron emission tomography measurement using [¹¹C]doxepin ([¹¹C]DOX) to evaluate histamine H₁ receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [¹¹C]DOX, estimated quantitatively with a two-compartment model, and the [¹¹C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [¹¹C]DOX–H1R binding.     

Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H-[13C]-NMR spectroscopy.

Localized, water-suppressed (1)H-[(13)C]-NMR spectroscopy was used to detect (13)C-label accumulation in cerebral metabolites following the intravenous infusion of [1,6-(13)C(2)]-glucose (Glc). The (1)H-[(13)C]-NMR method, based on adiabatic RF pulses, 3D image-selected in vivo spectroscopy (ISIS) localization, and optimal shimming, yielded high-quality (1)H-[(13)C]-NMR spectra with optimal NMR sensitivity. As a result, the (13)C labeling of [4-(13)C]-glutamate (Glu) and [4-(13)C]-glutamine (Gln) could be detected from relatively small volumes (100 microL) with a high temporal resolution. The formation of [n-(13)C]-Glu, [n-(13)C]-Gln (n = 2 or 3), [2-(13)C]-aspartate (Asp), [3-(13)C]-Asp, [3-(13)C]-alanine (Ala), and [3-(13)C]-lactate (Lac) was also observed to be reproducible. The (13)C-label incorporation curves of [4-(13)C]-Glu and [4-(13)C]-Gln provided direct information on metabolic pathways. Using a two-compartment metabolic model, the tricarboxylic acid (TCA) cycle flux was determined as 0.52 +/- 0.04 micromol/min/g, while the glutamatergic neurotransmitter flux equaled 0.25 +/- 0.05 micromol/min/g, in good correspondence with previously determined values.