新型心肌显像剂[99Tcm(N)(PNP5)(DBODC)]+猪心肌显像研究

目的 评价新型心肌显像剂[99Tcm(N)(PNP=5)(DBODC)]+在猪体内的药代动力学特征及生物分布特性.方法 利用药盒法制备[99Tcm(N)(PNP5)(DBODC)]+注射液.实验动物选7头实验用成年健康中华小型猪,由耳静脉注入[99Tcm(N)(PNP5)(DBODC)]+,分别于注射后2,5,10,15,30,45,60,75,90,120,150和180 min从猪后肢静脉进行血样采集以获得药代动力学参数,同时进行胸腹部平面系列显像,以观察该药物在猪体内的生物分布和靶/非靶比值,并与99Tcm-甲氧基异丁基异腈(MIBI)显像比较(采用配对t检验).结果 [99Tcm(N)(PNP5)(DBODC)]+标记率为(95.54±0.85)%,其符合一次静脉给药的药代动力学二室模型,分布半衰期T1/2á=(2.97±0.48)min,消除半衰期T1/2a=(52.49±19.49)min,血液总清除速率(CL)=(14 314.29.±8445.79)ml/h.心、肝、肺时间-放射性曲线显示[99Tcm(N)(PNP5)(DBODC)]+肝摄取在初始时明显高于心肌,但肝内放射性清除迅速,在注射30 min后,肝内放射性已低于心肌放射性,而99Tcm-MIBI肝摄取在180 min内均高于心肌.[99Tcm(N)(PNT5)(DBODC)]+的心/肝比值在注射后30～180 min均高于99Tcm-MIBI(t值为10.395～54.482,P均＜0.05).显像示在注射[99Tcm(N)(PNP5)(DBODC)]+后5～180 min均可获得清晰的心肌图像,肝内示踪剂迅速排入胆、肠系统,致使肝内放射性迅速减低,有利于减少对左室下壁的干扰.结论 [99Tcm(N)(PNP5)(DBODC)]+有望成为一种新的心肌灌注显像剂.     

99 Tcm-HYNIC-Annexin V荷瘤小鼠肿瘤细胞凋亡显像研究

目的研究99Tcm-联肼尼克酰胺-膜联蛋白V(HYNIC-Annexin V)的制备及其在荷瘤小鼠体内生物分布特性和活体显像.方法用双功能螯合剂法,以99Tcm标记Annexin V,经高效液相色谱仪分离纯化并检测产物的标记率、放化纯及稳定性.建立荷S180肉瘤小鼠模型,于20～25g/只昆明种小白鼠右前腋皮下接种S180肉瘤细胞1周.荷瘤小鼠在环磷酰胺腹膜内化疗72h后,尾静脉注射7.4 MBq(200μl)99Tcm-HYNIC-Annexin V,分别于5、30min和1、3、6 h进行显像和体内生物分布测定.实验结果应用SPSS 12.0统计软件进行分析.结果 99Tcm-HYNIC-Annexin V的标记率达95%,放化纯为99%.荷瘤小鼠注射99Tcm-HYNIC-Annexin V后6 h显像,可见肿瘤组织放射性浓聚明显异常.体内生物分布实验示,注射显像剂后6 h肿瘤组织的放射性摄取最高[每克组织百分注射剂量率(%ID/g)为1.59±0.44],与其他时相比较,差异有显著性(P＜0.05).99Tcm-HYNIC-Annexin V主要浓聚于肾、肺和肝,经肾脏排泄;其在血液中清除速度快,注射后30 min,血液放射性摄取[(1.59±0.50)%ID/g]较注射后5 min时[(8.85±2.65)%ID/g]减少80%(P＜0.05).注射显像剂后6 h,肿瘤/肌肉放射性摄取比值(3.73±1.42)高于肿瘤/血液(2.80±0.54).结论 99Tcm-HYNIC-Annexin V活体细胞凋亡显像可应用于荷瘤小鼠模型,其临床应用有待进一步研究.     

肺动脉血栓放射免疫显像实验研究

目的　通过动物实验探讨肺动脉血栓放射免疫显像在肺栓塞诊断及血栓性质鉴别中的价值。方法　选取杂种犬 7只 ,制成肺动脉血栓栓塞模型。静脉注射99Tcm 标记的活化血小板单克隆抗体SZ 5 1,进行活体γ显像。完整取出心肺后行离体心肺显像。分别观察血栓部位及周围组织的放射性分布 ,计算栓塞部位与周围组织的放射性比值。随后取出血栓及周围部分组织 ,称重后测定单位质量的放射性计数及单位质量血栓与周围组织的放射性比值。结果　注入显像剂后 1h ,血栓部位开始显影并逐渐清晰。新鲜血栓放射性摄取明显高于周围肺组织 ,注入显像剂后 3h ,活体显像和完整心肺离体显像新鲜血栓与周围肺组织的放射性比值分别为 2 .8± 0 .6和 3.5± 1.2。形成 1d的新鲜血栓的放射性摄取明显高于形成 1周左右的血栓 ,单位质量新鲜血栓与周围组织的放射性比值达 17.5± 1.3,是形成 1周左右血栓的 2 .6倍。结论　99Tcm SZ 5 1肺动脉血栓放射免疫显像对诊断急性肺栓塞的形成及鉴别新鲜与陈旧血栓具有较好的应用前景。     

多层螺旋CT肺动脉造影联合静脉造影诊断深静脉血栓的研究

目的应用16层螺旋CT肺动脉造影联合静脉造影(CTVPA)探讨深静脉血栓发生率及部位,并与下肢彩色超声多普勒对照评价其诊断下肢深静脉血栓(DVT)的价值。方法临床怀疑肺栓塞(PE)的147例病人行CTVPA检查,以病人为单位计算两医师诊断DVT一致性;102例患者同时行下肢超声检查,计算股静脉-腘静脉段DVT诊断敏感度、特异度、阳性预测值、阴性预测值。结果147例患者中33例(22.4%)有DVT,27例合并PE。33例DVT的患者CTV共发现156个部位的血栓,腹盆腔静脉血栓共48个(31%),股静脉-腘静脉段血栓58个(37%),小腿静脉血栓50个(32%)。DVT血栓CT值为(42±13)HU。2医师诊断DVT的一致率为90%,Kappa值为0.86。以超声作为对照,CTV诊断股静脉-腘静脉段DVT的敏感度为92.3%,特异度为100%。结论CTV对股静脉-腘静脉段DVT诊断准确率高,并能显示下腔静脉、滤器内及盆腔静脉血栓,CTV的观察者间诊断一致性非常好。     

一日法99Tcm-替曲膦运动-静息门控心肌灌注显像的临床研究

目的 探讨使用亚锡替曲膦药盒能否得到满足临床需要的99Tcm-替曲膦(TF)以及1d内完成99Tcm-TF运动-静息G-MPI的可行性.方法 回顾性分析52例行99Tcm-TF运动-静息G-MPI且均有CAG结果的受试者资料.标记亚锡替曲膦并进行放化纯检测.1d内对受试者分别在运动负荷及静息状态下静脉注射99Tcm-TF 370和740 MBq,30 min时行G-MPI.2次注射显像剂间隔时间为(129±4)min.运动负荷状态下注射99Tcm-TF后加行1～ 30 min前位胸腹部平面动态显像和2h前位平面显像.用ROI技术分析胸腹部平面动态像,得到左室心肌、肝及胸部放射性变化情况;用Cedars心肌定量分析软件分析左室心肌各节段灌注情况及左室功能参数(LVEF、EDV、ESV等).1周内行超声心动图检查,获取LVEF、EDV和ESV.对运动-静息G-MPI(取2次显像平均值)心功能参数与超声心动图结果采用SPSS 17.0进行配对t检验.结果 99Tcm-TF放化纯为(97.5±0.4)％.G-MPI左室心肌显影清晰;动态显像示左室心肌与肝放射性比值12 min后逐渐增大,30 min时达0.710,2h延迟显像左室心肌内放射性基本清除.以CAG为“金标准”,G-MPI诊断心肌缺血的灵敏度为84.6％ (22/26),特异性为92.3％(24/26);G-MPI与超声心动图测定的LVEF、EDV和ESV分别为(60.27±7.49)％和(60.84±5.98)％,(97.82±18.98)ml与(98.70-±17.89) ml,(47.67 ±10.32) ml与(45.49 ±10.15) ml,差异均无统计学意义(t=1.254、0.835和0.981,P均＞0.05).结论 采用亚锡替曲膦药盒标记得到的99Tcm-TF能够满足临床需要;99Tcm-TF能够在1d内完成运动负荷及静息G-MPI,可作为常规评价心肌灌注及左室功能的显像剂.     

下肢静脉病变与肺动脉栓塞关系的研究

目的 探讨下肢静脉病变与肺栓塞（PE）发病之间的关系。方法 对50例正常对照者和200例临床高度怀疑PE和下肢静脉病变的患者,行^99Tc^m-大颗粒聚合白蛋白（MAA）和^99Tc^m-葡聚糖酯（GP）双下肢静脉显像和肺灌注/通气显像,其中15例进行了肺动脉造影。结果 对照组下肢静脉显像和肺灌注/通气显像均显示正常,200例患者肺灌注/通气显像示：175例为多发性PE,25例正常。175例PE患者中128例有下肢静脉病变,占73.14%（128/175例）,其中下肢深静脉血栓（DVT）119例,占68.00%（119/175例）;25例非PE者均有下肢静脉病变。153例下肢静脉病变者中检出PE128例,占83.66%(128/153例）。下肢DVT 119例,其中由髂、股静脉血栓引发PE者101例,占84.87%（101/119例）。结论 双下肢静脉显像与肺灌注/通气显像联合应用,有助于PE及其病因的诊断。     

靶向整合素αvβ3探针用于甲状腺乳头状癌显像的研究

目的 制备特异性整合素αvβ3探针[^18F]氟化铝-匹仑吉肽（^18F-Al-NOTA-PRGD2）,探讨其用于甲状腺乳头状癌（PTC） PET显像的可行性.方法 采用氟化铝新策略制备18F-Al-NOTA-PRGD2.取新鲜切除的人PTC肿瘤组织接种于裸鼠右腋下,制得荷人PTC裸鼠模型.再分别取人PTC标本及毗邻的正常组织、荷瘤裸鼠移植瘤行整合素αvβ3免疫组织化学染色.荷瘤裸鼠（n=5）尾静脉注射1.1 MBq ^18F-Al-NOTA-PRGD2后30、60和120 min分别行microPET显像,通过ROI技术计算肿瘤和主要脏器的放射性摄取值（％ ID/g）,并通过阻断实验验证其特异性.另取15只荷瘤裸鼠研究其注药后30、60及120 min生物分布,计算放射性摄取值（％ID/g）.用两样本t检验进行统计学处理.结果 成功制备^18F-Al-NOTA-PRGD2,标记率＞45％.免疫组织化学染色证实人PTC标本和裸鼠移植瘤组织整合素αvβ3染色均呈棕褐色阳性表达,人PTC毗邻正常组织不表达.荷瘤裸鼠注射^18 F-Al-NOTA-PRGD2后行microPET显像示,肿瘤清晰可见,且与周围组织对比度良好.注射后30、60、120 min肿瘤对显像剂的摄取值分别为（2.81±0.35）、（2.45±0.27）和（1.80±0.21） ％ID/g.PRGD2阻断后,注射^18F-Al-NOTA-PRGD2后60 min肿瘤对显像剂的摄取值降为（0.51±0.05） ％ID/g.荷瘤裸鼠生物分布实验示,注射显像剂后30、60、120 min肿瘤摄取值分别为（3.09±0.25）、（2.75±0.37）和（1.90±0.16） ％ID/g,与microPET显像基本一致（t=1.456、1.465和0.847,均P＞0.05）.^18F-Al-NOTA-PRGD2在血液和肌肉中清除快,注射后60 min肿瘤与血液和肌肉的摄取比值分别为6.15±0.45和7.86±0.56.结论 ^18F-Al-NOTA-PRGD2制备简单,放化纯高,可有效监测PTC中整合素αvβ3表达水平;其PET显像有望为研究PTC整合素αvβ3受体相关机制提供一种新方法.     

99Tcm-大颗粒聚合白蛋白显像在下肢深静脉血栓中的诊断价值

目的 探讨99Tcm-大颗粒聚合白蛋白( 99Tcm-M AA)核素深静脉显像(RNV)对下肢深静脉血栓(DVT)的诊断价值.方法 临床疑似下肢DVT的患者45例,均行99Tcm-MAA双下肢RNV,并与临床最终诊断结果进行对照.结果 43例共51条患肢经临床确诊,51条血栓性患肢中,左下肢36条、右下肢15条,左下患...     

甲状旁腺腺瘤摄取高锝酸盐一例

患者女,74岁,因血钙和PTH升高,临床诊断为甲状旁腺功能亢进症.实验室检查:血钙2.89(正常参考值2.0～2.7) mmol/L,PTH 224(正常参考值15～65)ng/L.甲状腺超声提示左叶甲状腺下极1.3 cm×0.7 cm低回声结节,怀疑甲状旁腺腺瘤可能,于本科行甲状旁腺显像.患者分别行99Tcm-MIBI/99TcmO:双显像剂减影法和99Tcm-MIBI双时相法甲状旁腺显像(99Tcm-MIBI与99TcmO:均购自北京森科医药有限公司,显像仪器为荷兰Philips SKYLight SPECT).患者经静脉注射99TcmO4-37 MBq,20 min后行甲状腺动态显像,再注射99Tcm-MIBI 740 MBq,20 min后行动态显像,并在注射后20 min及2h分别行99Tcm-MIBI静态显像.     

99Tcm-Ap4A显像探测动脉粥样硬化斑块的动物实验研究

目的探讨应用二磷酸腺苷(ADP)的类似物99Tcm-四磷酸二腺苷(Ap4A)显像探测动脉粥样硬化斑块的可行性.方法采用酒石酸亚锡还原99TcmO-4标记Ap4A,柱层析纯化,纸层析鉴定放射化学纯度.观察99Tcm-Ap4A在昆明小鼠体内的生物分布并测定动脉粥样硬化模型家兔病灶斑块/血液、病灶斑块/无斑块动脉壁的放射性比值,进行腹主动脉宏观放射自显影及正常家兔及动脉粥样硬化家兔体外体内显像.结果99Tcm-Ap4A的放射化学纯度为85%～91%.99Tcm-Ap4A在小鼠血液内清除迅速.注射99Tcm-Ap4A后30min粥样硬化组靶/血比值达3.17±1.27,靶/非靶比值为5.23±1.87.粥样硬化组自显影胶片上的曝光黑影与肉眼可见的动脉粥样硬化斑块有良好的一致性.体外显像正常家兔组腹主动脉未显影,粥样硬化组腹主动脉放射性浓聚清晰可见.体内显像粥样硬化组家兔的腹主动脉在注射99Tcm-Ap4A后15～30min与正常家兔组相比放射性浓聚明显增强,并持续到注药后3h.结论99Tcm-Ap4A是一种有潜力的可快速显示动脉粥样硬化斑块形成的显像剂.     

99锝m N-2-巯基吡啶-N-氧化物与99锝m-甲氧基异丁基异腈对犬急性心肌梗死模型的对照研究

目的 在正常和心肌梗死犬模型上,研究99TcmN-2-巯基吡啶-N-氧化物(99TcmN-MPO)的药物代谢动力学特征、生物学分布特征和对急性心肌梗死的诊断能力,并与传统示踪剂99锝m-甲氧基异丁基异腈(99Tcm-MIBI)进行对比研究.方法 正常杂种犬12只.静脉注射99TcmN-MPO,于不同时间点(30 s及1、2、3、4、5、10、20、30、40、60和90 min)静脉分别采血1 ml,经γ探测器测量其放射活性;注药后10、20、30、60、90及120 min行全身SPECT显像,并于不同器官上各取同样大小的ROI,测量其放射性计数进行定量研究.每只犬均注射相同剂量的99TcmMIBI,进行相同的实验作为对照.介入学方法构建犬急性心肌梗死模型,24 h后,静脉注入99TcmN-MPO(5只)和99Tcm-MIBI(5只),并于注药后30、60min进行心肌SPECT显像.结果 在静脉注射90 min内,99TcmN-MPO和99Tcm-MIBI均表现为快速的血液清除.两种示踪剂的初始注射剂量均为370 MBq.注射后1 min,每毫克血浆的放射活性小于初始注射剂量的50%[99TcmN-MPO为(35.77±6.31)%ID/mg;99Tcm-MIBI为(34.46±6.83)%ID/mg],30 min时＜5%[99TcmN-MPO:(3.11±1.44)%ID/mg;99Tcm-MIBI:(2.93±0.39)%ID/mg].99TcmN-MPO在心脏的浓聚明显,且存留时间很长,由于其在肝脏清除的速度较快,因此可获得良好的心/肝摄取比值,注射后10 min为0.54±0.06,30 min为1.02±0.06,60 min上升到1.38±0.06.相比之下,99Tcm-MIBI的心/肝摄取比值上升较为缓慢(注射后10 min为0.46±0.03,30 min为0.63±0.03,60 min为0.62±0.12).犬心肌梗死后SPECT心肌断层扫描显示,在注射99TcmN-MPO 30 min后,心脏与肝脏分界清楚,可清楚显示心肌缺血、梗死灌注缺损区域、范围和程度;而99Tcm-MIBI注射后60 min,心脏和肝脏的分界依然不清,尤其是肝脏的高放射性对心脏下壁和左心室壁的影响很大,对心脏左心室壁的心肌梗死灌注缺损区域的显示不佳.结论 99TcmN-MPO具有心肌摄取量较高,肝脏代谢快的特点,是一种具有广阔临床应用前景的SPECT心肌灌注成像显像剂.

Abstract：

Objective The purpose of the present study is to compare the pharmacokinetic and biodistribution properties of 99Tcm N-mercaptopyridine-N-oxide (99 Tcm N-MPO) with 99 Tcm-sestamibi (99 Tcm-MIBI) in normal dogs, and to investigate the potential of 99TcmN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Methods Twelve healthy mongrel dogs were injected intravenously with 99TcmN-MPO (n = 6) or 99Tcm-MIBI (n = 6). Tracer kinetics in body fluids were determined by collecting blood of 1 ml via a femoral vein catheter at 30 s, 1,2,3,4,5, 10, 20, 30, 40, 60and 90 min post-injection (p. i.). The collected blood samples were weighed and counted for radioactivity in a γ-counter. Anterior and posterior planar γ-camera images were collected at 10, 20, 30, 60, 90, and 120 min after injection, with organ uptake quantified by region-of-interest (ROIs) analysis. For comparison, 99Tcm-MIBI was also evaluated in the same twelve dogs. Canine infarct models were set up by micro-invasive interventional embolization. SPECT images in the canine infarct model were collected 24 hours after myocardial infarction at 30 min and 60 min after the administration of 99Tcm N-MPO (n = 5) or 99Tcm-MIBI (n = 5). Results Both of 99Tcm N-MPO and 99Tcm-M1BI had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min [99TcmN-MPO: (35. 77 ± 6. 31)% ID/mg ,99Tcm-MIBI (34. 46 ± 6. 83) % ID/mg] and less than 5% at 30 min p. i. [99Tcm N-MPO(3. 11 ± 1.44) % ID/mg,99Tcm-MIBI (2.93 ±0. 39)% ID/mg] . After injection, 99TcmN-MPO showed significant accumulation in the myocardium and prolonged retention. This rapid liver clearance of 99TcmN-MPO led to favorable heart-to-liver ratios, reaching values of 0. 54 ±0. 06 at 10 min, 1.02 ±0. 06 at 30 min, and 1.38 ±0. 06 at 60 min p. i.In contrast, the heart/liver ratio of 99Tcm-MIBI remained low at all time points (0. 46 ± 0. 03 at 10 min,0. 63 ±0. 03 at 30 min, and 0. 62 ± 0. 12 at 60 min p. i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of 99TcmN-MPO, but not 99Tcm-MIBI. Conclusion The combination of high heart uptake and rapid liver clearance makes 99TcmN-MPO a promising new radiotracer for myocardial perfusion imaging.     

新型骨显像剂99Tcm-BIPrDP的制备及生物学性质研究

目的 探讨99Tcm-1-羟基-3-(2-丁基-1H-咪唑-1-基)丙烷-1,1-双膦酸(BIPrDP)用于骨显像的可能性.方法 以2-丁基咪唑为原料,经过3步反应得到BIPrDP.以SnCl2为还原剂,在100℃下沸煮BIPrDP钠盐溶液(50 mg/ml,100μl)与新鲜淋洗的Na99TcmO4溶液(37.0 MBq)混合液30 min,制得99Tcm-BIPrDP.用TLC测定标记率和稳定性.测定99Tcm-BIPrDP在正辛醇-水中的脂水分配系数(log P)和在新鲜肝素抗凝的人血血浆中的血浆蛋白结合率.向ICR小鼠尾静脉注射0.2 ml (7.4 MBq) 99Tcm-BIP(r)DP,分别在5、10、15、30、60、120和240 min时处死小鼠,取其心、肝、脾、肺、肾、骨骼、肌肉、性腺、肠、胃、脑和血液,测其质量及放射性计数,计算％ ID/g及骨放射性与各组织中放射性的比值.计算血药清除动力学方程.对新西兰兔静脉注射99Tcm-BIPrDP后于不同时问显像.用单因素方差分析方法对不同时间各组织％ID/g进行统计学分析.结果 99Tcm-BIPrDP的标记率和放化纯均＞95％,在放置6h后仍具有很好的稳定性.99Tcm-BIPrDP在pH值为7.0和7.4时的log P分别为-2.396 ±0.035和-2.242±0.025,99Tcm-BIPrDP的血浆蛋白结合率为(47.07±0.05)％.在注射99Tcm-BIPrDP 30 min后小鼠骨摄取达到最大值(19.20％ID/g),且能持久,在4h时为18.98％ID/g.在所有的非靶向性组织中,99Tcm-BIPrDP在肾的摄取最高,5min时为24.50％ID/g,4h为5.22％ID/g.其他重要器官普遍摄取较低,在4h时肌肉和脑最低,分别为0.18 ％ID/g和0.03 ％ID/g.在5 min时99Tcm-BIPrDP在血液中的摄取为18.60％ID/g,随后迅速降低,在4h时仅为0.40％ID/g,血药动力学方程为C ＝9.109e-0.262t+2.696e-0.00558t.从药物清除曲线可看出该药在小鼠体内血液清除速率较快,与小鼠体内分布中的血液清除趋势一致.注射99Tcm-BIPrDP后1h即可获得清晰的兔骨显影,在其他软组织中摄取低,清除快.各组织不同时间％ ID/g差异有统计学意义(F=5.65 ～ 859.24,P均＜0.05).结论 99Tcm-BIPrDP制备方便,骨显影清晰,是一种较有潜力的新型骨显像剂.     

Imaging thromboembolism with fibrin-avid 99mTc-peptide: evaluation in swine.

A pentapeptide, Gly-Pro-Arg-Pro-Pro, with high affinity for alpha-chain-fibrin was labeled with (99m)Tc ((99m)Tc-TP850) and evaluated in swine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE). METHODS: Scatchard analysis was performed to determine fibrin affinity for TP850 and the number of binding sites (receptors) per milligram of fibrin. DVT was induced in the left jugular vein and PE was induced by introducing a preformed autologous blood clot into the right atrium using a 7-French introducer sheath inserted into the right jugular vein. (99m)Tc-TP850 was injected at 4, 24, 48, 72, 96, or 120 h later. Animals were imaged for up to 4 h after injection, heparinized, and sacrificed. Lungs were extirpated, radiographed, and imaged, and the PE was removed. Other tissues, including blood and normal lungs, were harvested and, concomitantly, (99m)Tc was counted for determination of target-to-tissue ratios and the percentage injected dose per gram of tissue. RESULTS: The affinity for human fibrin was 10(-9) mol/L and there were >10(15) receptors per milligram of fibrin. DVT and PE were visualized for up to 4 h after injection with high DVT/blood (7.9-22.6), DVT/muscle (31.1-89.4), PE/blood (1-155), and PE/lung (0.8-245) ratios. Thereafter, the PEs fragmented spontaneously below the spatial resolution of the gamma-camera and, despite the high associated radioactivity, could not be localized in vivo. The fragmented clots were detectable by scintigraphy on excised lungs and provided excellent concordance with radiograms. CONCLUSION: (99m)Tc-TP850 with its modest affinity (10(-9) mol/L), rapid blood clearance, and high DVT and PE uptake is a promising agent for imaging vascular thrombosis.     

S-11C-甲基-L-半胱氨酸在荷Hepa 1-6肝癌小鼠体内的分布及PET显像研究

目的 研究S-11C-甲基-L-半胱氨酸(11C-MCYS)在荷Hepa 1-6肝癌小鼠体内的生物学分布及其在肿瘤PET显像中的价值.方法 (1)荷Hepa 1-6肝癌小鼠25只,经尾静脉注射11C-MCYS注射液1.48 MBq,分别在注药后5、10、20、30和60 min5个时间点测量肿瘤组织及各器官的放射性,计算％ID/g.荷瘤小鼠10只,经尾静脉注射11C-MCYS 1.48 MBq,分别于5、10、20、30和60 min行全身PET/CT扫描,观察全身放射性分布及代谢情况.(2)荷瘤小鼠及炎性反应小鼠模型各20只,经尾静脉注射11C-MCYS 1.48 MBq,1h后行全身PET/CT扫描.通过ROI获得肿瘤和炎性反应组织的SUVmax,并计算肿瘤/肌肉、炎性反应组织/肌肉放射性比值.采用t检验进行统计分析.结果 (1)11C-MCYS在体内吸收迅速,给药后5 min放射性分布即可达到高峰,5 min时肝和肾放射性分布分别为(1.97±0.12)和(1.02±0.09) ％ID/g,60 min时肝和肾放射性摄取降为(0.53±0.14)和(0.29±0.05)％ID/g,而脑、肺、胃及肌肉等组织放射性摄取均小于(0.23±0.05)％ID/g,肿瘤组织放射性摄取为(0.48±0.05)％ID/g.荷瘤小鼠不同时间点PET显像示小鼠各脏器的放射性摄取与各相应时间点小鼠体内放射性分布一致.(2)肿瘤组织摄取11C-MCYS较高,SUVmax为4.58±0.65,而炎性反应组织摄取11C-MCYS较低,SUVmax为1.02±0.18,肿瘤/肌肉及炎性反应组织/肌肉的放射性比值分别为7.27和1.62,差异有统计学意义(t=2.906,P＜0.01).结论 11C-MCYS是一种有前景的新型氨基酸类PET显像剂,有望用于肿瘤与无菌性炎性反应的鉴别.     

99Tcm标记双半胱氨酸-脱氧葡萄糖的小鼠实验研究

目的研究^99Tc^m标记双半胱氨酸一脱氧葡萄糖(EGDG)在正常小鼠及荷S180肉瘤小鼠体内的分布规律。方法正常小鼠及荷S180肉瘤小鼠各铝只，分8组，实验前禁食。尾静脉注射^99Tc^m-EC-DG后计算不同时间在小鼠体内的分布及肿瘤与血液、肌肉、肺、肝的放射性比值。同时，取荷瘤小鼠5只，在注射后不同时间进行显像，计算T／NT比值。结果肿瘤组织与血液、肌肉、肺的放射性比值随时间延长逐渐上升，在4h都超过1．0。显像示随时间延长瘤体周围组织放射性逐渐下降，瘤体在4h时显影清晰。结论^99Tc^m-EC-DG可用于肿瘤的葡萄糖代谢显像。     

Imaging vascular thrombosis with 99mTc-labeled fibrin alpha-chain peptide.

An agent that permits scintigraphic detection of chronic deep venous thrombosis (DVT) or pulmonary embolism (PE) would be a welcome addition to the armamentarium of nuclear medicine. Because fibrin is the integral part of each clot, old or fresh, we hypothesized that a 99mTc-labeled fibrin alpha-chain N-terminal peptide, Gly-Pro-Arg-Pro-Pro, that binds to the C-terminal portion of the gamma-chain of fibrin can detect DVT and PE. METHODS: The peptide was modified to Gly-Pro-Arg-Pro-Pro-Aba-Gly-Gly-(D)-Ala-Gly to permit efficient binding of 99mTc (99mTc-TP 850). The stability of the peptide was examined in vitro as well as in vivo. The ability of the agent to bind to rabbit, dog, and human fibrin and to inhibit adenosine diphosphate-induced platelet aggregation was examined. Blood clearance and 3-h tissue distribution were studied. DVT was induced in 8 rabbits using a stimulating electrode and in 2 rabbits by inserting a thrombin-soaked suture. PE was induced in 6 additional rabbits by introducing tantalum-impregnated blood clots into the right atrium, and the rabbits were radiographed to locate the emboli. 99mTc-TP 850 was then injected through a lateral ear vein, and each rabbit was imaged for up to 3 h. The rabbits were then killed, the heart and lungs were dissected and radiographed and the clots were harvested so that clot-to-blood radioactivity ratios could be determined. RESULTS: The peptide analog permitted efficient incorporation of 99mTc, which was stable in vitro and in vivo. The blood clearance was biphasic, with an alpha phase half-life of approximately 4 min (20%) and a beta phase half-life of approximately 13 min (88%). The mean binding of 99mTc-TP 850 to human, dog, and rabbit fibrin was 46% +/- 2%, 60% +/- 3%, and 56% +/- 2.5%, respectively, and the inhibitory concentration of 50% for dog and rabbit platelet aggregation was 236 pm and 167 pm, respectively. All clots, including 24-h-old pulmonary emboli, were delineated. The radioactivity associated with clots varied from 0.01 to 0.09 %ID/g, with clot-to-blood radioactivity ratios ranging from 1.2 to 12.0. However, 48-h-old pulmonary emboli had lysed and were seen neither by radiography nor by scintigraphy. CONCLUSION: A fibrin alpha-chain, N-terminal peptide that binds to the C-terminal portion of the gamma-chain of fibrin has been modified and labeled with 99mTc. The resultant peptide is stable in vitro and in vivo; binds to human, dog, and rabbit fibrin in large quantities; and inhibits platelet aggregation. The peptide clears rapidly from the blood and delineates experimental DVT and PE in rabbits. This agent is worthy of further investigation.     

Evaluation of 99mTc-dextran as a lymphoscintigraphic agent in rabbits

Dextran (clinical grade, average mol. wt. 82,200) was labelled with 99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free 99mTcO-4 was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200-600 microCi/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12% +/- 0.77% to 4.28% +/- 1.57% at 3 and 2 h, respectively (P less than 0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that 99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.     

^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。     

钆双胺对^99Tc^m—MDP骨显像影响的实验研究

目的探讨MRI对比剂钆双胺注射液（欧乃影;Gd—DTPA—BMA）应用后对家兔^99Tc^m-MDP骨显像的影响。方法采用自身前后对照方法,实验组（注射欧乃影＋^99Tc^m-MDP）与自身对照组（注射生理盐水＋^99Tc^m-MDP）处理相隔7d。（1）取家兔5只,注射欧乃影或生理盐水后30min注射^99Tc^m-MDP,并于注射^99Tc^m-MDP后5、10、30、60、120、180、240和360min、24h时行骨显像,勾画ROI,计算靶／本底（T／B）值,观察家兔显像剂分布及代谢情况。（2）取家兔30只,按欧乃影或生理盐水与^99Tc^m-MDP的注射间隔（30、60、120、240和360min、24h）分为6组,每组5只。均于注射^99Tc^m-MDP后120min行骨显像,勾画ROI,计算T／B值。（3）采用TLC测定2种药物相互作用后在体内的放化纯差异。以配对t检验进行统计分析。结果注射欧乃影后30min再注射^99Tc^m-MDP,5min时肝、脾开始显影,其T／B比值120min时达最高峰（肝、脾分别为4．56±0．32和3．56±0．41）;而2组椎体24h时T／B值均达最大值（实验组为4．32±0．07,自身对照组为6．31±0．09）,但各时间点实验组均较自身对照组低。两药物注射间隔为30、60、120和240min时,可出现肝、脾异常显影,对应的实验组T／B（肝：2．47～4．22;脾：1．85～3．23）明显高于自身对照组（肝：1．52—1．58;脾：1．25～1．29）,但实验组椎体的T／B（3．08～4．28）则较自身对照组低（4．82～4．85）,以上差异均有统计学意义（t=7．750—31．916,均P〈0．05）。余时间间隔组,肝、脾未见明显摄取^99Tc^m-MDP。TLC曲线示,实验组在Rf为0—0．2处形成小峰,^99Tc^m-MDP放化纯降为（63．51±2．24）％。结论注射欧乃影后短时间内行^99Tc^m-MDP骨显像,肝、脾会出现异常摄取;间隔360min再行^99Tc^m-MDP骨显像可避免此现象发生。     

68Ga-NOTA-Duramycin的标记与生物分布实验研究

目的 制备68Ga-1,4,7-三氮杂环壬烷-1,4,7-三乙酸-耐久霉素(NOTA-Duramycin),探讨其在小鼠体内生物分布及在评价猪心肌缺血再灌注损伤模型心肌细胞凋亡中的价值.方法 采用固相法合成NOTA-Duramycin,再于常温下标记、合成68Ga-NOTA-Duramycin,用HPLC法测定其标记率和放化纯,观察标记物体外稳定性及在正常小鼠体内的生物分布.制备猪心肌缺血再灌注损伤模型(n=6),注射68Ga-NOTA-Duramycin 37.0 MBq后1h,行PET/CT显像,探测心肌细胞凋亡;显像结束后,将其处死,取其心脏行凋亡病理分析.结果 68Ga-NOTA-Duramycin标记率为(92.5±2.1)％,放化纯＞90％,体外稳定性好.正常小鼠体内生物分布实验显示,早期相(5 min)68Ga-NOTA-Duramycin在血液、心、肝、脾、肺和肾的放射性摄取分别为(23.50±15.38) ％ID/g、(8.53±4.52) ％ID/g、(8.26±2.24) ％ID/g、(2.12±0.28) ％ID/g、(5.02±1.46) ％ID/g和(50.62±54.24)％ID/g,延迟相(60 min)放射性摄取分别降为(1.83±0.31) ％ID/g、(1.05±0.31) ％ID/g、(0.97±0.28) ％ID/g、(0.68±0.27) ％ID/g、(2.15±0.90) ％ID/g和(8.12±2.74)％ID/g,表明该显像剂主要经肾排泄.在猪心肌缺血再灌注损伤模型中,68Ga-NOTA-Duramycin PET/CT湿像示缺血心肌部位呈局灶性放射性浓聚,病理证实该缺血部位有大量心肌细胞发生凋亡.结论 68Ga-NOTA-Duramycin标记方法简单,反应条件温和,稳定性好,可有效探测猪心肌缺血再灌注损伤模型的心肌细胞凋亡,有望成为一种新型细胞凋亡显像剂.