国产锝[99Tcm]替曲膦注射液临床验证研究

目的 研究锝[99Tcm]替曲膦注射液一步法新药盒用于心肌灌注显像的效果及安全性.方法 采用随机、双盲、平行、对照设计.以习用的心肌灌注显像剂99Tcm-甲氧基异丁基异腈(MIBI)为锝[99Tcm]替曲膦的对照药物.确定入选者符合标准并签署知情同意书后,进行双嘧达莫(潘生丁)负荷和静息心肌显像.观察心肌显像前后的生命体征和有无不良反应.由2位核医学科医师双盲判读心肌显像图并对图像质量作出评价.结果 100例病例人组锝[99Tcm]替曲膦心肌显像(试验)组,108例入组99Tcm-MIBI对照组.所有病例均未观察到使用心肌显像药物引起的不良反应.试验组100例均获得合格的心肌影像并足以提供诊断依据,心肌影像质量良好.与对照组相比,心肌影像质量没有明显差异.结论 锝[99Tcm]替曲膦注射液标记简便,制剂稳定,心肌影像图像质量优良,且使用安全.     

~(99)Tc~m-人血清白蛋白:一种有效的识别黑色素瘤前哨淋巴结的放射性示踪剂

前哨淋巴结 ( SL N )活检是证实黑色素瘤和局部淋巴结微小转移的一种新方法。99Tcm-硫胶体 ( 99Tcm- SC)是最初用来观察肿瘤淋巴引流的类型和 SL N定位的显像剂。99Tcm-人血清白蛋白 ( 99Tcm - HSA)是一种分子量小、制备简单、引起过敏的可能性小的淋巴显像示踪剂 ,它能否取代 99Tcm- SC呢 ?为此 ,比较了基于 99Tcm - HSA显像的 SL N活检与基于 99Tcm -SC显像的 SL N活检的效能。方法 :选择 10 6例皮肤黑色素瘤的患者 ,85例患者行99Tcm - HSA显像 ,2 1例行 99Tcm - SC显像。有 4例患者行两种淋巴显像 ( 99Tcm- HSA和 99Tc…     

99Tcm-MIBI诊断重度淤胆型婴儿肝炎综合征的价值

目的 鉴于99Tcm-二乙基亚氨基二乙酸(99Tm-EHIDA)肝胆显像对临床重度淤胆患儿应用的局限性,试用99Tcm-甲氧基异丁基异腈(99Tcm-MIBI)作为新的肝胆显像剂,了解其应用基础及对重度淤胆患儿的初步诊断价值.方法 建立胆总管闭锁动物模型,了解99Tcm-MIBI肝胆显像的应用基础;对重度淤胆并最终临床证实为婴儿肝炎综合征的27例患儿先行常规99Tcm-EHIDA肝胆显像,次日行24 h延迟显像,1 h后再行99Tcm-MIBI肝胆显像.比较两种显像剂对重度淤胆型婴儿肝炎综合征的诊断价值.结果 动物实验证明,99Tcm-MIBI确经肝胆排泄,且无明显肠道自分泌现象,可以用作肝胆显像.初步临床诊断表明,99Tcm-MIBI肝胆显像对重度淤胆型婴儿肝炎综合征的诊断灵敏度达100%,远远高于常规99Tcm-EHIDA肝胆显像(66.67%).结论 对临床高度怀疑的重度淤胆型婴儿肝炎综合征,99Tcm-MIBI肝胆显像的诊断灵敏度明显高于常规99Tcm-EHIDA肝胆显像.     

用2-IT修饰单抗SZ-51制备~(99)Tc~m-IT-SZ-51血栓显像药盒

目的　研究99Tcm 标记抗P 选择素单克隆抗体SZ 5 1血栓显像药盒的制备方法。方法用 2 亚氨基噻吩盐酸盐 (2 IT)修饰SZ 5 1。用99Tcm 葡庚糖酸钠转换络合标记法标记IT SZ 5 1,测定标记物的放化纯度及生物活性 ,以最佳标记条件制备体内血栓显像药盒。结果　以最佳比例修饰SZ 5 1,每分子抗体游离巯基数为 13个 ,纸层析法测得标记率大于 90 % ,酶联免疫吸附测定结果表明标记物保留了抗体的免疫活性。制成的药盒 4℃条件下可保存 3个月。结论　该标记方法简便快速     

188Re(Ⅴ)-DMSA药盒制备及其质量评估

目的研制188Re(Ⅴ)-二巯基丁二酸(DMSA)标记配方并制备药盒,评价药盒的质量.方法酸性环境下,SnCl2·2H2O还原高价态ReO4-为Ⅴ价,并与DMSA反应,制备药盒,以高压液相色谱仪(HPLC)测定该药盒的标记率、标记物的体外稳定性、药盒的稳定性,并与99Tcm(Ⅴ)-DMSA在小鼠体内分布比较.结果药盒标记率为100%,标记物室温放置24 h后标记率＞97%;药盒置-20和4℃条件下3个月后,标记率＞95%;188Re(Ⅴ)-DMSA与99Tcm(Ⅴ)-DMSA在小鼠体内分布相似,在骨骼高浓聚,经肾脏排泄.结论188Re(Ⅴ)-DMSA药盒性能优良.     

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.     

新生儿胆道闭锁~(99)Tc~m-EHIDA显像应注意的几个问题

放射性核素肝胆显像是一种简便无创的检查方法 ,对先天性胆道闭锁 (BA)的诊断准确性可达 95 % [1 ] 。笔者用西门子e CamSingleSPECT仪 ,对 17例疑似BA患儿静脉注射99Tcm 二乙基乙酰苯胺二氨二醋酸 (EHIDA ,江原制药厂提供 ) 37～74MBq进行核素肝胆显像 ,并与临床表现、实验室检查及手术结果对比。显像诊断BA 14例 ,手术确诊 12例 ,诊断准确性为 85 71% ,3例诊断为婴儿肝炎综合征 (IHS) ,经临床治疗后恢复。回顾上述工作 ,有几方面问题应引起注意 ,现阐述如下。1 显像剂的选择。目前常用的肝胆显像剂有乙酰替苯胺亚氨二醋酸 (IDA)类化合物 (如EHIDA)和三甲基溴类化合物 (如mebrofenin)等。其分子结构、脂溶性等基本能满足①血液清除快 ;②肝胆通过时间短 ;③胆管系统显影清晰 ;④经肾脏排出少。IDA类化合物受血中胆红素的影响较大 ,经肝多角细胞摄取进入肝细胞 ,且与胆红素有相同的肝脏摄取和排泄过程。因此两者间存在竞争抑制作用 ,血清胆红素高达一定程度时可使IDA类化合物进入肝细胞的量大大降低[1 ] ,影响胆道系统显影清晰度。因此...     

生长抑素受体显像剂99Tcm-奥曲肽的SPECT研究

核医学SPECT在20世纪已进入分子显像时代,受体显像尤其是生长抑素受体显像更是目前核医学显像研究的热点.利用111In、123I、99Tcm、90Y等放射性核素标记生长抑素类似物奥曲肽进行生长抑素受体显像的方法,已经比较成熟,且部分已用于临床显像.该文对99Tcm标记奥曲肽的方法(直接法、间接法)、99Tcm-奥曲肽SPECT显像方法及其临床应用等作简要概述.     

99Tcm-HMIBP的生物学特性及与99Tcm-MDP的骨显像比较

目的 通过99Tcm-1-羟基-2-(1-甲基咪唑-2-基)乙烷-1,1-二膦酸(HMIBP)和鲫99Tcm-亚甲基二膦酸盐(MDP)的骨显像质量比较,评价99Tcm-HMIBP作为骨显像剂的可能性.方法 制备HMIBP冻干药盒,对HMIBP及SnCl2-2H2O含量、放化纯、药盒pH值及在4℃下的稳定性等进行了研究.测定99Tcm-HMIBP在正辛醇/水相中的分配系数(P)及血浆蛋白结合率,计算血药清除动力学方程参数.同时研究了HMIBP的半数致死剂量(LD50).新西兰兔静脉注射99Tcm-HMIBP和99Tcm-MDP后同步显像比较.结果 99Tcm-HMIBP药盒含HMIBP 5 mg,SnCl2·2H2O 0.05 mg,药盒pH值为5,标记率和放化纯均为98%;在4℃下放置180 d后标记率为96%.在pH值为7.0和7.4时,P值分别为0.0125和0.0054,血浆蛋白结合率为44.77%.小鼠血药清除动力学方程为C=3.0979 e-0.0721t+0.1250 e-0.0076.HMIBP的LD50为8.2 mg/kg.兔骨显像表明,99Tcm-HMIBP和99Tcm-MDP在3 h时均可获得清晰的图像.结论 99Tcm-HMIBP生物学性能优良,显像效果与99Tcm-MDP相当,可能成为集显像与治疗于一体的骨显像剂.     

99Tcm-环丙沙星炎症显像的动物实验研究

目的 用99Tcm标记环丙沙星并评估其生物学性能.方法 制备99Tcm-环丙沙星,测定其稳定性,并研究其在健康昆明小鼠体内和在炎症模型昆明小鼠及新西兰兔体内的分布.结果 99Tcm-环丙沙星标记率＞90%,6 h内放化纯均＞98%.99Tcm-环丙沙星静脉注射后主要分布在血供丰富的器官,如肾、肝、脾中.血液清除快,主要经泌尿系统排泄.新西兰兔炎症模型显像表明:注射99Tcm-环丙沙星1 h后即可显影;给药后3 h为炎症小鼠模型最佳显像时间,此时炎症组织/肌肉放射性比值为5.76.99Tcm-环丙沙星能高度特异地浓聚于细菌性炎症病灶.结论 99Tcm-环丙沙星是早期诊断细菌性炎症的一种特异性显像剂,其临床应用前景较好.     

99Tcm-DTPA-DG的制备及其荷瘤裸鼠实验研究

目的进行99Tcm-DTPA-脱氧葡萄糖(DG)的化学合成、标记物制备、质量控制及药理研究.方法合成的DTPA-DG用氯化亚锡作还原剂,与99TcmO4-混合,在25℃以上室温放置30 min或沸水浴反应10nin,用一步法进行99Tcm标记.丙酮和质量分数0.9%生理盐水作展开剂,用纸层析法鉴定99Tcm-DTPA-DG的放化纯、标记稳定性;进行乳腺癌MCF-7裸鼠体内生物分布实验及显像研究.结果标记产物放化纯＞99%.99Tcm-DTPA-DG荷瘤裸鼠生物分布显示,肿瘤/血液比值1、2 h分别为1.29、3.13,肿瘤/肌肉比值1、2 h分别为2.63、5.01.荷瘤裸鼠99Tcm-DTPA-DG显像显示肿瘤组织.结论99Tcm-DTPA-DG可能成为肿瘤葡萄糖代谢显像剂.     

Citrin缺陷所致新生儿肝内胆汁淤积症的99Tcm-EHIDA肝胆动态显像

目的 研究citrin缺陷导致的新生儿肝内胆汁淤积症(NICCD)99Tcm-EHIDA肝胆动态显像特点及临床价值.方法 分别对NICCD组(12例)和NICCD阴性对照组(5例,4例婴儿肝炎综合征和1例脂类代谢异常)患儿[年龄分别为(127±27)d和(164±15)d]进行99Tcm-EHIDA肝胆动态显像,观察注射显像剂后肝脏及肠道放射性分布,并采用秩和检验比较2组肝影持续时间及肠道显影时间.结果 NICCD组肠道显影时间和肝影持续时间均在180～1440min(中位数均为360min),而对照组肠道显影时间在15～30min(中位数为15min),肝影持续时间在60～180min(中位数为60min).NICCD患儿肝影持续时间及肠道显影时问均明显延长(Z=-3.20和-3.17,P均＜0.05).3例NICCD患儿肝显影不清晰,其中1例NICCD患儿胆囊及肠道在24h内始终未见显影,治疗后该患儿肝胆动态显像示肝摄取及排泄功能明显改善,15min肠道显影.结论 99Tcm-EHIDA肝胆动态显像示NICCD患儿肝脏摄取和排泄功能降低,提示99Tcm-EHIDA肝胆动态显像在NICCD诊断中可作为辅助检查手段.     

乏氧组织显像剂99Tcm-DTPA-甲硝唑的制备和荷瘤动物实验研究

目的　进行新型乏氧组织显像剂DTPA 甲硝唑的化学合成、药盒制备、99Tcm 标记、质量控制以及药理研究。方法　合成的DTPA 甲硝唑用氯化亚锡作还原剂 ,99Tcm 标记 ,用多元正交法确立99Tcm 标记一步法药盒的最佳配方。纸层析法鉴定99Tcm DTPA 甲硝唑的标记率、标记稳定性 ,完成了H2 2肝癌小鼠体内生物分布实验及显像研究。结果　DTPA 甲硝唑一步法药盒与99TcmO-4 混合 ,沸水浴反应 10min ,放化纯度大于 99%。H2 2肝癌小鼠生物分布显示 ,肿瘤 /血液比值 1、2h分别为3 43、6 40 ,肿瘤 /肌肉比值 1、2h分别为 5 2 4、7 42 ;注射血管舒张药肼苯哒嗪组肿瘤组织摄取明显高于对照组 (P <0 0 1)。结论　研制的99Tcm DTPA 甲硝唑有望成为一种新型的肿瘤乏氧组织显像剂。     

Synthesis and evaluation of a technetium-99m-labeled diethylenetriaminepentaacetate-deoxyglucose complex ([99mTc]-DTPA-DG) as a potential imaging modality for tumors.

This study describes the radiolabeling and preliminary biologic testing of diethylenetriaminepentaacetic acid (DTPA)-deoxyglucose (DG) labeled with (99m)Tc. A one-step [(99m)Tc]-DTPA-DG kit was prepared using the stannous chloride reduction method. When (99m)TcO(4)(-) was added to the DTPA-DG kit at room temperature the radiochemical purity 30 min later was 99.2%, and it remained >98.6% for 6 h. Rapid blood clearance of [(99m)Tc]-DTPA-DG was observed in in vivo biodistribution, the main route of clearance was via the kidneys. No significant accumulation in any other organs was seen. The tumor-to-brain and tumor-to-muscle concentration ratios for [(99m)Tc]-DTPA-DG uptake were higher than those for fluorine-18-flurodeoxyglucose ((18)F-FDG). Scintigraphic results demonstrated the feasibility of [(99m)Tc]-DTPA-DG imaging tumors. The [(99m)Tc]-DTPA-DG complex is a potential imaging agent due to the ideal physical characteristics of the radionuclide, ease of preparation, low cost, early accumulation and the preference for the renal route of excretion.     

多巴胺转运蛋白显像剂^99Tc^m—TRODAT-1药盒及注射液的质量控制

目的对自制多巴胺转运蛋白显像剂^99Tcm-TRODAT-1药盒及注射液进行质量控制研究。方法对3批^99Tc^m-TRODAT-1药盒及注射液进行澄清度、pH值、氯化亚锡与TRODAT-1含量、标记率、放化纯、半衰期测定,无菌以及细菌内毒素检查,可见异物、不溶性微粒检查,并分析药盒在不同存放环境下的稳定性。结果^99Tc^m-TRODAT-1药盒澄清度好,pH值为5．9±0．1,药盒中氯化亚锡与TRODAT-1含量稳定,标记率大于95％。药盒在0-4℃下6个月、室温（20～25℃）下10d内稳定性好。注射液澄清透明、pH值在5．5～7．0之间,放化纯≥95％,室温（20～25℃）下8h内放化纯〉90％。药盒及注射液无菌、细菌内毒素检查合格。结论自制的^99Tc^m-TRODAT-1药盒及注射液的质量控制方法简便易行,药盒及注射液质量符合临床应用要求。     

胆囊炎及结石性胆囊炎99Tcm-EHIDA

目的　探讨胆囊炎及结石性胆囊炎胆囊显像特点。方法　对 14例无肝胆疾病的正常对照者和均经手术病理检查证实的包括胆囊炎患者 2 7例、结石性胆囊炎患者 38例 2个疾病组进行了99Tcm 二乙基乙酰苯胺基亚氨二乙酸 (EHIDA)肝胆显像及半定量分析。结果　与对照组比较 ,2个疾病组潜伏期 (LP)延长 ,胆囊排胆分数 (EF)及排胆率 (ER)均明显降低 ,差异均有高度显著性 (P均 <0 0 1)。胆囊平均排空曲线示 2个疾病组脂餐后胆囊排空潜伏期延长 ,呈“再充盈”现象。急性胆囊炎及慢性胆囊炎急性发作 6例、慢性胆囊炎 8例以及结石性胆囊炎 2 0例胆囊未见显影。结论　核素肝胆显像可早期预测胆囊疾病的发生并指导治疗     

Technetium coordination state as a factor of stability in 99mTc-complexes used in hepatobiliary system: Comparative studies on 99mTc-complexes of pyridoxal with glutamate (Tc-PG) and isoleucine (Tc-PI)

Studies on ^99mTc-Penicillamine (Tc-Pen) have given us some insight into the significance of the technetium coordination state in hepatobiliary clearance behavior.A ^99mTc-complex of pyridoxal and glutamate (Tc-PG) prepared by Baker et al. (1975) using an autoclaving process or by a Sn-Resin kit method (Horiuchi 1981) was compared with a ^99mTc-complex of pyridoxal and isoleucine (Tc-PI) prepared by the method of Kato and Hazue (1978) through an intermediate compound of stannous ion, at room temperature.Tc-PG and TcPI complexes analyzed by thin layer chromatography, sephadex column chromatography (G-15), octanol extraction, and ligand exchange reaction showed different chemical properties. Their biological evaluation also demonstrated great differences in biodistribution in mice, metabolic studies, protein binding, and rat bile excretion.Tc-PG was estimated as an hepatobiliary agent with strong metal-ligand binding, inert to ligand exchange reaction with Pen at physiological pH; the likely occurrence of technetium in a mononuclear or dinuclear state providing the great stability observed in its biological and in vivo behavior was compared with the relatively weaker binding observed in Tc-PI, a highly lipophilic complex of high liver partition but of low stability, denoting its different chemical characteristics.The technetium coordination state in radiopharmaceuticals is responsible for the integrity of the molecule while in the blood pool and its relevance in impaired liver uptake is discussed.     

Technetium-99m d,l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion

Following investigation of a large number of new ligands based upon propylene amine oxime (PnAO) the d,l-diastereoisomer of hexamethyl propyleneamine oxime (HM-PAO) was selected as the preferred ligand for 99mTc as a tracer for cerebral perfusion imaging. The neutral, lipophilic 99mTc complex of d,l-HM-PAO was formed in high yield by stannous reduction of 99Mo/99mTc generator eluate using a kit formulation of the ligand. Two minutes following i.v. administration of this complex in rats, 2.25% of the injected dose appears in the brain. Little washout of the tracer is observed up to 24 hr postinjection. By qualitative autoradiographic comparison with iodoantipyrine this new radiopharmaceutical displays blood flow dependent brain uptake with little redistribution of the tracer over time. The lipophilic 99mTc complex converts slowly in vitro to a secondary complex. This conversion process may account for the ability of [99mTc]d,l-HM-PAO to be retained within the brain without redistribution.     

Analysis of 99mTc-pyridoxylidene-glutamate complex formation and its preparation with tin-adsorbed-resin: Sn-resin kit method

^99mTc-Pyridoxylidene-glutamate (Pc-PG) was introduced in 1975 by Baker et al. as a cholescintigraphic agent. Nevertheless its routine use has been limited due to the autoclaving process involved. To shorten the labeling procedure, an analysis of Tc-PG complex formation using the stannous chloride method was carried out. Sn-Resin (stannous ion adsorbed onto cation exchange resin) was used for labeling a stable Tc-PG with high efficiency. A preautoclaved complex of pyridoxal and glutamate was required but the labeling procedure took only 10–15 min after the elution of ^99m-TcO ₄ ^- from the generator.Formation of a complex other than a ^99mTc-complex of the Schiff-base ligand pyridoxylidene-glutamate is discussed.The new formulation of a Tc-PG kit (Sn-Resin) simplified the labeling method and reproducible data to that already reported by Baker was obtained in chromatographic studies. Its suitability in hospital departments has already been shown in clinical studies.     

Technetium-99m labeling of a molecule bearing easily reducible groups

Chemical stability of the naphthol-azo dye Evans Blue (EB) was examined in the presence of acidic stannous chloride (SnCl₂), with a view to preparing an instant cold kit. EB was found to be reactive toward this reducing agent, yielding the metal-chelating molecule 1,7-diamino-8-naphthol-2,4-disulfonic acid at high acidity and high stannous concentrations. This reduction reaction was undesirable in the cold kit preparation. The conditions were determined where reduction was inhibited, at pH = 5.0 and with a mole ratio of EB to SnCl₂ = [10:1], effecting the facile preparation of stable cold kits. Successful ^99mTc-labeling of an EB cold kit using these conditions resulted in the desired product with 98% radiochemical purity. Based on the radiolabeling efficiencies of chosen model compounds, it was rationalized that ^99mTc metal predominantly coordinated with the 1-amino-8-hydroxy groups in the EB molecule to form ^99mTc-EB.