^99Tc^m标记RGD环肽在荷肺腺癌裸鼠中的显像研究

目的制备^99Tc^m标记的含RGD序列的^99Tc^m-联肼尼克酰胺（HYNIC）-c（RGDfK）环肽单体,评价其在整合素表达阳性的肺腺癌严重联合免疫缺陷（SCID）小鼠肿瘤模型中的生物学分布,并进行显像研究。方法（1）以HYNIC为双功能螯合剂,以三羟甲基甘氨酸（tricine）和乙二胺二乙酸为协同配体,采用二步法制备^99Tc^m标记HYNIC—c（RGDfK）,进行细胞结合实验,测定标记物生物学活性;（2）将荷A549肺腺癌模型小鼠分为7组[第7组作为竞争性抑制组,注射显像剂前0．5h先注射HYNIC-c（CRDGfk）100μg],每组5只,经尾静脉注射7．4MBq的^99Tc^m-HYNIC-c（RGDfK）,于注射后0．5,1,2,4,8,12h处死,计算荷A549肺腺癌小鼠模型各脏器％ID／g,同时采用ROI技术研究^99Tc^m-HYNIC—c（RGDfK）在小鼠体内的生物学分布,计算不同时间点的T／NT比值（NT选取肌肉）;（3）取6只荷瘤裸鼠,其中3只为竞争性抑制组,经尾静脉注射7．4MBq的^99Tc^m-HYNIC—c（RGDfK）,于注射后0．5,1,2,4,8,12h进行静态1显像。结果^99Tc^m-HYNIC—c（RGDfK）的标记率〉90％,放化纯〉95％。^99Tc^m-HYNIC—c（RGDfK）与A549肺腺癌细胞特异性结合率最高为36．14％,体内分布实验显示^99Tc^m-HYNIC—c（RGDfK）在肾的摄取率始终高于20％ID／g,注射后0．5h肿瘤％ID／g为10．52±1．48,8h为17．26±2．81,12h为8．93±0．90,竞争性抑制组注射后0．5h为2．29±0．85。通过ROI技术测得T／NT在8h达6．87。注射后1h肿瘤可显影,4～8h显影更清晰。结论^99Tc^m标记HYNIC—c（RGDfK）易于制备,具有良好的靶向性。     

99Tcm-c-myc mRNA反义肽核酸荷结肠癌裸鼠显像

目的 制备99Tcm-c-myc mRNA反义肽核酸(PNA)显像探针,通过反义显像研究99Tcm-c-myc mRNA反义PNA早期诊断结肠癌的可行性.方法 利用化学合成法在c-myc mRNA反义PNA片段的5'端连上4个氨基酸[G-(D)-A-G-G]和1个氨基丁酸(Aba),再利用配体交换法对c-myc mRNA反义PNA行99Tcm标记.并用同样的方法制备99Tcm-c-myc mRNA无义PNA.进行人结肠癌LS174-T荷瘤裸小鼠显像.采用SAS 6.12软件进行统计学处理.结果 99Tcm-c-myc mRNA反义PNA 6h内标记率＞95%.血清孵育5h后标记率为91.1%.无义PNA的标记率与反义PNA基本一致.1h时反义组荷瘤裸鼠右后肢肿瘤部位可清晰显影,4h内未见明显变化.无义组肿瘤部位始终未见明显放射性摄取.注射99Tcm-c-myc mRN反义PNA 1h后,反义组与无义组肿瘤与对侧组织的放射性(T/N)比值分别为5.06±1.35和1.53±0.30,差异有统计学意义(t=4.47, P=0.04).结论 99Tcm-c-myc mRNA反义PNA可在荷瘤裸鼠活体内与高表达c-myc基因的人结肠癌LS174-T肿瘤组织特异结合,在肿瘤反义显像中有潜在的应用价值.     

99Tcm-J591的制备及荷人前列腺癌裸鼠显像

目的 研究99Tcm-抗前列腺特异性膜抗原(PSMA)抗体J591与前列腺癌细胞体外结合性能、在荷人前列腺癌裸鼠显像及体内分布情况.方法 用改进的Schwarz方法进行99Tcm标记J591,经Sephadex G-50柱分离纯化;用纸层析法和三氯醋酸法测定标记率与放化纯;用流式细胞术测定99Tcm-J591与肿瘤细胞在体外的结合性能.以PSMA阳性的C4-2前列腺癌荷瘤裸鼠为实验组,PSMA阴性的PC3前列腺癌荷瘤裸鼠为对照组,2组均经静脉注射99Tcm-J591 6.2～ 8.5 MBq(25 μg/只)后,分别于2、6、12及24h后行γ显像,利用ROI技术获得各时间点T/NT(NT为对侧肌肉组织).12 h显像后分批处死裸鼠(实验组4只,对照组5只),取肿瘤、心、肝、肾、胃、骨骼、肌肉和血液等组织,测湿质量和放射性计数,计算％ID/g,采用两样本t检验比较2组间差异.结果 99Tcm直接标记J591的标记率为(78.9±6.2)％,放化纯为(92.3±5.1)％,放射性比活度为68.7 MBq/mg.流式细胞术分析结果显示,J591与99Tcm-J591在体外均能结合PSMA阳性的C4-2细胞,与PSMA阴性的PC3细胞不结合.实验组静脉注射99Tcm-J591后6h,肿瘤部位出现明显放射性浓聚,至12 h放射性浓聚范围增大,边缘更清晰,2、6、12和24 h T/NT分别为1.9±1.1、4.3±1.8、5.6±2.7和1.4±0.6;对照组肿瘤部位未见明显放射性浓聚,各时间点T/NT均小于2.体内分布结果显示:注药后12 h,实验组肿瘤放射性为(20.1±5.2) ％ID/g,对照组为(5.8±2.6)％ID/g,两者差异有统计学意义(t=5.37,P＜0.001);其余部位2组间放射性摄取差异无统计学意义(均t＜1.98,均P＞0.05).结论 99Tcm-J591具有良好的免疫活性和生物分布特性,对接种于裸鼠体内的人前列腺癌具有靶向定位性能,可望用于前列腺癌的导向诊断及导向治疗.     

99Tcm-（HYNIC-[Lys3]-BBS）（tricine）（tricine）的制备及对胰腺癌荷瘤鼠显像研究

目的制备99Tcm-（联肼尼克酰胺-蛙皮素类似肽）（N-三羟甲基甘氨酸）（三苯基膦三间磺酸钠盐）[（HYNIC-[Lys3]-BBS）（tricine）（TPPTS）]三重配位化合物,评价其在正常小鼠及胰腺癌荷瘤裸小鼠的生物分布。方法双功能螯合剂HYNIC与[Lys3]-BBS偶联（pH值9．0）,以SnCl2为还原剂,tricine和TPPTS为协同配体,进行99Tcm-标记,合成三重配位化合物99Tcm-（HYNIC-[Lys。]-BBS）（tricine）（TPPTS）。用Sep-PakC18cartridge和HPLC对其纯化和分析,测定其标记率和放化纯,研究其在人血清中的稳定性,并进行正常小鼠体内的生物分布研究以及胰腺癌荷瘤裸小鼠活体显像。结果99Tcm-（HYNIC_[Lys3]-BBS）（tricine）（TPPTS）标记率为（90±2）％,放化纯〉95％,在人血清中放置4h其放化纯仍大于85％。正常小鼠体内分布结果表明,99Tcm-（HYNIC-[Lys3]-BBS）（tricine）（TPPTS）血液清除迅速,2h血液中放射性为（0．07±0．01）％ID／g,主要经。肾排泄,肝、胃肠道摄取较少,2h时肝放射性为（0．27±0．03）％ID／g,胃为（0．06±0．03）％ID／g,肠为（0．04±0．00）％ID／g。胰腺癌荷瘤裸小鼠吖显像可见肿瘤部位有放射性浓聚影,2h后肿瘤与对侧正常肌肉的T／NT比值最高达3．71±0．57。结论99Tcm-（HYNIC-[Lys3]-BBS）（tricine）（TPPTS）三重配位化合物制备成功,所用标记方法可行,标记物稳定性较好,标记率和放化纯较高,生物分布特性良好,有望用于胰腺癌的显像研究。     

99Tcm标记抗人粒细胞单抗SZ-102在荷人胰腺癌裸鼠的显像研究

目的研究^99Tc^m标记抗人粒细胞单克隆抗体SZ-102在荷人胰腺癌裸鼠体内显像及生物分布。方法以2-亚氨基噻吩盐酸盐(2-IT)修饰SZ-102，^99Tc^m-葡庚糖酸钠(GH)配体交换法标记SZ-102，经裸鼠尾静脉注入^99Tc^m-SZ-102后4、8和24h分别测定荷瘤小鼠体内组织的放射性分布，并于1和4h对裸鼠进行γ显像。结果γ显像及生物分布示，^99Tc^m-SZ-102静脉注入荷瘤鼠后1h，肿瘤清晰显影，随时间延长，瘤体内放射性越来越浓，且瘤组织与非瘤组织的放射性比值(T／NT)也逐渐增高，各时相肿瘤每克组织百分注射剂量率(％ID／g)高于注射^99Tc^m-IgG的对照组。结论^99Tc^m-SZ-102具有活体内定位导向能力，显像时间短。     

99Tcm—survivinmRNA反义肽核酸制备及荷瘤裸鼠基因显像研究

目的制备99Tcm标记的survivinmRNA反义肽核酸（PNA）探针,并进行荷瘤裸鼠体内基因显像,研究其对肿瘤早期诊断的价值。方法化学合成survivinmRNA的反义、无义PNA,在5’端连上4个氨基酸[Gly一（D）Ala—Gly—Gly],形成1个类似N。结构的强螯合基团;为消除空间阻碍,引入1个1一氨基丁酸（Aba）作为隔离物,利用配体交换法进行99Tcm标记。用HPLC及ITLC对标记物的标记率、放化纯进行鉴定。并对反义、无义组各5只人肺癌A549荷瘤裸鼠行99Tcm一survivinmRNA反义、无义PNA体内显像。注药后1,2和4h分别显像,利用ROI测得肿瘤与对侧组织的rr／NT比值。结果分析采用SPSS13．0软件进行成组t检验。结果99Tcm一survivinmRNA反义PNA即刻标记率为（95．48±1．92）％,放化纯〉95％,且标记物体外稳定性好,与血清保温24h后标记率仍〉85％。无义PNA标记率与之基本一致。99Tcm一survivinmRNA反义PNA在肿瘤组织内特异性浓聚,随时间延长,浓聚程度逐渐增加,1,2和4hT／NT值分别为2．70±0．28,3．44±0．35和4．21±0．63。无义PNA在肿瘤组织中稍有浓聚,但在4h内变化不大,4h时T／NT值（3．12±0．50）与反义组差异有统计学意义（t=2．918,P：0．019）。结论99TcmsurvivinmRNA反义PNA即刻标记率高,稳定性好,无需纯化即可用于显像,在肿瘤组织中特异性浓聚,对肿瘤的早期诊断有潜在价值。     

68Ga-DOTA-NOC胰腺癌生长抑素受体靶向显像的实验研究

目的 研究68 Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-1-萘丙氨酸-奥曲肽(DOTA-NOC)在小鼠体内的生物分布,并进行荷胰腺癌小鼠的68Ga-DOTA-NOC SSTR靶向显像.方法 37 MBq 68GaCl2加入20μl羟乙基哌嗪乙硫磺酸(HEPES,0.1 mmol/L)溶液和10～50 μg DOTA-NOC,于95℃水浴加热15 min制备68Ga-DOTA-NOC.采用HPLC法分析68 Ga-DOTA-NOC的标记率及体外稳定性.予正常BALB/c小鼠尾静脉注射68Ga-DOTA-NOC 3.7 MBq,分别在5、15、30、60和120 min后解剖分离小鼠脏器,测放射性生物分布(％ID/g)情况.将人CFPAC-1胰腺癌细胞与68Ga-DOTANOC共同孵育后,测定放射性计数并计算摄取率.建立CFPAC-1荷瘤裸鼠模型,行microPET显像,勾画ROI,获得肿瘤及主要脏器TAC,计算T/NT(NT为对侧肌肉).用流式细胞术检测CFPAC-1细胞及瘤体SSTR表达水平,采用直线相关分析对SSTR表达率与T/NT行相关性研究.结果 68 Ga-DOTA-NOC标记率为(98.8±1.0)％,无需纯化.正常小鼠体内68Ga-DOTA-NOC肾摄取最多,5 min为(11.20±0.32) ％ID/g,随时间延长减少,60 min为(4.11±0.21)％ID/g,胰腺、肺、胃相对摄取较高,脑几乎无摄取.人CFPAC-1细胞可特异性摄取68Ga-DOTA-NOC.荷瘤鼠microPET显像示CFPAC-1肿瘤部位呈异常放射性摄取,T/NT在120 min达3.2±0.2.CFPAC-1细胞和肿瘤组织SSTR1、2、4、5表达量分别为(96.83±1.23)％、(99.73±0.98)％、(90.42±0.63)％和(92.96±0.71)％,SSTR2、5的表达水平与T/NT均呈正相关(r=0.71、0.80,均P＜0.05).结论 68 Ga-DOTA-NOC易标记,生物分布理想,可靶向结合SSTR阳性的CFPAC-1肿瘤组织.68Ga-DOTA-NOC是新型SSTR靶向显像剂,有利于胰腺肿瘤的早期诊断并为生长抑素介导靶向治疗提供依据.     

双功能制剂99Tcm-Gd-DTPA-DG的制备及在荷瘤裸鼠体内的生物分布

Objective To evaluate the stability and biodistribution of a novel SPECT-MRI bi-functional agem 99Tcm-Gd-DTPA-DG in tumor-bearing nude mice. Methods DTPA-DG was synthesized and then conjugated with Gd2O3 to generate Gd-DTPA-DG. The tumor-bearing nude mice were scanned by MRI to evaluate the tumor targeting ability of Gd-DTPA-DG. The orthogonal experiment was applied to optimize pH value of reaction medium and reaction temperature. The radiolabeling efficiency was measured by thin layer chromatography. The distribution of 99Tcm-Gd-DTPA-DG in nude mice was evaluated by scintigrapy in vivo. The % ID/g was measured at different time after intravenous injection of 99Tcm-Gd-DTPA-DG. Results The tumor was significantly enhanced by Gd-DTPA-DG with MRI. The radiochemical purity of 99Tcm-Gd-DTPADG was about 98.5% and remained 96.2% at room temperature for 6 h. The tumor was well visualized by 99TcmGd-DTPA-DG SPECT at 2 h after injection. The tumor uptake was (1.48 ±0.12) %ID/g, and the rumor to muscle radioactivity ratio was 2.91. Conclusions MRI contrast of Gd-DTPA-DG may enhance tumor detection. 99Tcm-labeled Gd-DTPA-DG may be useful for tumor imaging and might have a potential role as a SPECT-MRI bi-functional agent.     

HER2放射性配体99Tcm-ABH2的制备及荷乳腺癌裸鼠显像

目的 制备99 Tcm-人表皮生长因子受体2(HER2)亲和体(ABH2),探讨其作为HER2阳性乳腺癌分子显像剂的可行性.方法 以葡庚糖酸钠和SnC12·2H2O为标记体系在ABH2上标记99Tcm,测定标记产物的标记率和放化纯,再用PBS和血清测定标记后6.0h内的稳定性.用表达HER2的MBA-MD-361乳腺癌细胞测定99Tcm-ABH2的平衡解离常数(Kd).于4只荷MBA-MD-361乳腺癌小鼠尾静脉注射37 MBq 99Tcm-ABH2,注射后1.0、4.5 h进行SPECT/CT显像,计算肿瘤对肝脏、大脑、肺、心脏、骨骼、肌肉的T/NT,2d后预先注射200 μg未标记的ABH2,再注射37 MBq 99Tcm-ABH2,以相同方法显像,应用单因素方差分析对比不同显像的T/NT.结果 99 Tcm-ABN2标记率在99％以上,其在PBS和血清中都稳定,在血清中37 ℃保温6.0 h放化纯达(95.0±1.0)％.99Tcm-ABH2的Kd为1.7 nmol/L.荷瘤鼠注射99Tcm-ABH2后1.0和4.5h显像见乳腺癌的放射性摄取,99 Tcm-ABH2主要从泌尿系统清除;4.5 h肿瘤对肝脏、肺、大脑、心脏、肌肉、骨骼的T/NT分别为1.81±0.60、8.95±1.13、20.08±6.12、7.61±0.56、10.62± 1.78、11.422.07;阻断后注射99Tcm-ABH2,4.5 h相应T/NT分别为0.60±0.23、3.05± 1.38、5.24±2.17、2.42± 1.02、8.16±2.66、2.76±0.48(F=29.38,P＜0.05).结论 成功制备了高纯度的99Tcm-ABH2,荷瘤鼠实验表明99Tcm-ABH2能够特异地对HER2阳性乳腺癌进行显像.     

99Tcm-RGD环肽二聚体的制备及其体内外评价

目的评价^99Tc^m标记的精氨酸-甘氨酸-天冬氨酸（RGD）环肽二聚体E[c（RGDfK）]：的体内外特性及其用于整合素α，B，阳性肿瘤显像的可行性。方法以三羟甲基甘氨酸（tricine）和三苯基膦三磺酸钠（TPPTS）作为协同配体，以联肼尼克酰胺（HYNIC）作为双功能连接剂，采用无亚锡一步法制备^99Tc^m-HYNIC—E[c（RGDfK）]：，通过U87人神经胶质瘤细胞测定其半数抑制浓度（IC50），观察其体外与整合素α，B，受体的结合解离动力学、细胞内化及外化，评价其在荷人神经胶质瘤裸鼠的生物分布。结果^99Tc^m-HYNIC-E[c（RGDfK）]，的标记率〉95％，经Sep-PekC18柱纯化后其放化纯〉99％。与RGD环肽单体C（RGDyK）相比，HYNIC偶联的E[C（RGDfK）]：二聚体具有更高的整合素α，β3亲和力，IC50分别为80．0和9．07nmol／L。细胞实验显示，^99Tc^m-HYNIC—E[C（RGDfK）]：与整合素α，β，结合较快，并迅速被受体介导内化。生物分布实验显示，^99Tc^m -HYNIC—E[C（RGDfK）]：主要经肾脏排泄，在注射后0．5和4h，标记物在肿瘤的每克组织百分注射剂量率（％ID／g）分别为（2．46±0．66）和（3．10±0．35）％ID／g，标记物在肿瘤中的滞留时间足够长。1显像示注射后1h肿瘤清晰可见，注射后4h显像效果更佳。结论^99 Tc^mHYNIC-E[C（RGDfK）]：是一种有前景的用于整合素α，β3，阳性肿瘤显像的显像剂。     

^99Tc^m-精氨酸-谷氨酸-苏氨酸在荷人肺癌H1299裸鼠体内分布和显像

目的通过研究^99Tc^m-精氨酸-谷氨酸-苏氨酸（RET）在荷人肺癌H1299裸鼠体内的分布及显像,探讨其用于肺癌显像的可行性。方法采用^99Tc^m-直接法标记RET,再行^99Tc^m-RET与NSCLC细胞H1299的结合实验。荷人肺癌H1299裸鼠尾静脉注射^99Tc^m-RET后,行不同时间（15、30min,1、2．4、8、24、48h组各4只鼠）体内分布实验,分别测定组织放射性摄取（％ID／g）;另取荷瘤鼠3只,注射4．81MBq^99Tc^m-RET后于0．5、1、2、4．5、5、6h行γ显像。结果^99Tc^m-直接标记RET的标记率为（93．15±2．02）％,与H1299细胞的最高结合率为（3．56±0．37）％。荷瘤裸鼠尾静脉注射^99Tc^m-RET后4h肿瘤放射性摄取达（4．96±1．05）％ID／g,肝脏、脾脏有较多放射性摄取[（15．89±1．84）％ID／g和（10．83±1．66）％ID／g];而心脏和血液的放射性摄取较少,相应的T／NT分别为5．70±0．21和12．40±0．11。注射^99Tc^m-RET后4．5～6．0h肿瘤显影清晰。结论^99Tc^m-RET具有亲肺癌的特性,有可能成为一种亲肺癌显像剂。     

Comparison of urokinase and tissue plasminogen activator for thrombolysis in rats

Microvascular thrombosis in free flap and replantation surgery may be amenable to thrombolytic therapy. A blinded, controlled, preliminary study in rats compared urokinase (UK) and tissue plasminogen activator (t-PA) on thrombolytic efficacy, systemic fibrinolytic effect, and reocclusion. Bilateral femoral vein clots were induced in 38 rats. Local infusion of UK, t-PA, or saline was performed. Fibrinogen levels were drawn from one group. A second group was evaluated for reocclusion up to one month. Ipsilateral lysis occurred for reocclusion up to one month. Ipsilateral lysis occurred in 10/12, 13/13, and 0/13 of the UK, t-PA, and saline groups, respectively, with no significant difference detected between the UK and t-PA groups. Contralateral clot lysis occurred in both the UK and t-PA groups. No significant differences in the fibrinogen levels was detected among the three groups. Reocclusion occurred only in the UK group.     

99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice

BACKGROUND AND AIM: Previous studies have showed that 99mTc labelled glucarate (GLA) might be an agent for non-invasive detection of breast tumours. In xenografted BT20 breast tumours, GLA was found to have higher uptake than 99mTc sestamibi (MIBI). It is unclear whether GLA can localize in all cell line breast cancer xenografts, as well as breast tumours with multidrug resistance (MDR). The present study aimed to investigate the properties of GLA in detecting drug sensitive and drug resistant MCF7 breast cancer xenografts in mice by using dynamic single photon emission computed tomography (SPECT) imaging. METHODS: MCF7/S cells are drug sensitive breast carcinoma cells. MCF7/D40 cells are 40-fold more resistant to doxorubicin compared to MCF7/S. Subcutaneous tumours were grown in SCID mice for 10-14 days after injection of 1 x 10(6) cells into the right thigh. Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT. Dynamic images were acquired for 2 h after intravenous injection of GLA or MIBI. Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours. RESULTS: The xenografted tumours were visualized unequivocally within 10-30 min in GLA images and remained detectable for at least 2 h after injection. Drug resistant tumours, from which MIBI was rapidly expelled, retained GLA as readily as did drug sensitive tumours. The biodistribution data of GLA demonstrated significantly higher accumulation (%ID/g) compared to MIBI. CONCLUSION: MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mTc glucarate can potentially localize drug resistant breast tumours.     

Tc-99m labeled tissue-type plasminogen activator: Preparation,stability and preliminary imaging of thrombus-bearing rats

Tissue-type plasminogen activator (t-PA) is a thrombolytic agent that directly binds to fibrin formed in clots. In terms of radiolabeling and nuclear imaging, t-PA has several advantages in Tc-99m labeling: it is stable in acidic solution at pH 3, which is suitable for labeling Tc-99m by a method of stannous reduction and blood disappearance after administration is rapid, which is desirable for imaging targets using short-lived radionuclides. Recombinant t-PA was labeled with Tc-99m by a method of stannous reduction without significant degradation of biochemical activity, over 95% of which was retained after the labeling procedure. Labeling efficiency in paper chromatography was over 98%. The moiety of hydrolyzed Tc-99m that was not eluted through the Sephadex column was estimated to be less than 10%. Tc-99m labeled t-PA, however, appeared to become unstable when diluted with normal saline. Nevertheless, in in vitro fibrin binding, Tc-99m labeled t-PA showed high affinity with fibrin: 80% of 100 ng/ml of Tc-99m t-PA bound to 10(-5) mol of the fibrinogen. Preliminary animal studies also showed a concentration of Tc-99m labeled t-PA at fresh thrombi formed in the inferior vena cava. Tc-99m labeled t-PA appears to have potential for thrombus imaging and the preparation of an instant kit.     

99Tcm-MIBI显像在头颈部恶性肿瘤中的应用

99Tcm-MIBI(99Tcm-sestamibi)作为亲肿瘤显像剂,对头颈部恶性肿瘤及其颈部淋巴结转移、邻近颅骨受累的诊断有较高的灵敏度、特异性和准确性,在头颈部肿瘤的诊断和分期等方面有良好的应用前景.     

重组型纤溶酶原激活剂与尿激酶在急性心肌梗死溶栓治疗中的比较

目的比较小剂量重组型纤溶酶原激活剂（rt-PA）与尿激酶（UK）溶栓治疗急性心肌梗死（AMI）的疗效和安全性。方法回顾42例接受rt-PA和49例接受UK溶栓治疗的AMI患者病例资料,对结果进行比较分析。结果冠脉总再通率rt-PA组和UK组分别为85．71％和61．22％（P〈0．05）;患者在发病3h和3—12h内溶栓,冠脉再通率在rt-PA组为94．11％和80．00％（P〉0．05）,在UK组为70．00％和58．97％（P〉0．05）;出血并发症rt．PA组和UK组分别为9．52％和10．20％（P〉0．05）。结论rt-PA的溶栓冠脉再通率显著高于UK,并且两组在发病后3h内较3h后溶栓均能取得更高的冠脉再通率,但无统计学差异。     

Sequential combination of intravenous recombinant tissue plasminogen activator and intra-arterial urokinase in acute ischemic stroke

BACKGROUND AND PURPOSE: Combined intravenous (IV) and intra-arterial (IA) thrombolytic therapy may be faster and easier to initiate than monotherapy, and its recanalization rate may be better as well. The sequential combination of recombinant tissue plasminogen activator (rTPA) and urokinase (UK) has synergistic and complementary effects on clot lysis. We prospectively evaluated the effectiveness and safety of sequential combination of IV rTPA and IA UK in acute ischemic stroke. METHODS: IV rTPA was administered to patients with acute stroke within 3 hours of onset. Those whose condition had not improved at the end of rTPA infusion were further treated with selective IA UK. We evaluated baseline and 30-day National Institutes of Health Stroke Scale (NIHSS) scores and 90-day modified Rankin Scale scores. RESULTS: Thirty patients were initially treated with IV rTPA; 24 were further treated with IA UK. Four patients who had rapid reocclusion following initial successful IA therapy received IV abciximab. Fourteen of 24 patients who underwent angiography had an effective perfusion state of Thrombolysis in Myocardial Infarction grade 3 flow. Median baseline and 30-day NIHSS scores were 18 and 2, respectively. Eighteen patients improved to a modified Rankin scale score of 0 or 1 after 90 days. Symptomatic hemorrhage developed in two patients. CONCLUSION: The strategy of using conventional-dose IV rTPA and the sequential combination of IA UK in patients without an early clinical response to IV treatment was safe and feasible. This strategy achieved high complete arterial recanalization rates and good functional outcomes.     

Comparison of tissue plasminogen activator and urokinase in the local infiltration thrombolysis of peripheral arterial occlusions

Recanalization of the vascular lumen by means of local fibrinolysis is of major importance in the treatment of peripheral arterial occlusive disease. While urokinase and streptokinase have been extensively used for local fibrinolysis, there have been few studies of infiltration thrombolysis with genetically engineered tissue plasminogen activator (rt-PA). The aim of the investigation reported here was to establish whether there is any difference between urokinase and rt-PA in the short- and long-term outcome of local fibrinolytic therapy. One- hundred twenty patients (70 men, 50 women) with acute or subacute femoral (n = 21), femoropopliteal (n = 33), popliteal (n = 13) or popliteocrural (n = 53) thrombotic occlusions were randomized to local lysis using urokinase or rt-PA, and 6 months later follow-up investigations took place. Recanalization of thrombotically occluded vessels, particularly in the lower leg, was found more frequently, and after treatment of shorter duration, with rt-PA. Large local haematomas occurred in 8% of cases in the urokinase group and 15% in the rt-PA group. No serious haemorrhages were encountered in either group. Six months after treatment, the rt-PA group showed lower rates of Fontaine stage III and IV disease and amputation than the urokinase group, with a higher number of patients in Fontaine stage IIb. This study shows that local lysis with rt-PA yields better results than urokinase, not only in the short term but also 6 months later.