^99mTc标记抗心肌肌凝蛋白单克隆抗体在实验性心肌梗塞中的研究

为比较＾９９ｍＴｃ－ＡＭＬＡ的特异性，将两组心肌梗塞２４ｈ大鼠分别注射＾９９ｍＴｃ－ＡＭＬＡ（ｎ＝２４）和＾９９ｍＴｃ－Ｎ－ＩｇＧ（ｎ＝１８），为研究不同心肌梗塞时间对摄取抗体的影响，将另一组不同心肌梗塞时间（２ｈ到１４ｄ共８个亚组）的大鼠注射＾９９ｍＴｃ－ＡＭＬＡ，计算三组的ＩＤ％／ｇ和梗塞心肌摄取／正常心肌摄取比（ＩＭ／ＮＭ）用一只心肌梗塞的狗注射＾９９ｍＴｃ－ＡＭＬＡ后离体心肌显像，结果表明     

^99mTc—MIBI评价缺血／再灌注心肌活力的实验研究

应用＾９９ｍＴＣ－ＭＩＢＩ对家兔缺血／再灌注心肌细胞及线粒体代谢和活力进行了评价，将家兔ＬＡＤ阻断２０ｍｉｎ，３ｈ再灌主，于灌注后２－５ｍｉｎ静脉注射＾９９ｍＴｃ－ＭＩＢＩ，结果缺血３ｈ组缺血心肌再灌注早期（１０ｍｉｎ）晚期（３ｈ）相对放射性活度，心肌ＡＴＰ含量均明显低于缺前２０ｍｉｎ组，非缺血心肌和缺血２０ｍｉｎ心肌＾９９ｍＴｃ－ＭＩＢＩ亚细胞分布与ＳＤＨ活性呈显著正相关（ｒ＝０．８８，Ｐ〈０．     

^99mTc直接法标记鼠／人嵌合抗体ccM4及在动物体内分布研究和初步临床…

ＳｎＣｌ２还原＾９９ｍＴｃＯ４后２－巯基乙醇还原的ｃｃＭ４混合标记。薄层层析测定标记率为９８％。ｃｃＭ４嵌合抗体标记前后免疫活性没有明显变化。动物体内分布实验结果显示：注射＾９９ｍＴｃ－ｃｃＭ４后１２ｈ，其放射性主要分布在肾，肝和血液；荷瘤鼠实验显示，％１２５Ｉ－ｃｃＭ４瘤体内聚集量最多。     

^99mTc标记环己二酮二肟及其甲基硼酸加成物和初步动物实验

实验结果表明，＾９９ｍＴｃ－ＣＤＯ的标记率受体系的ｐＨ值影响较小，而＾９９ｍＴｃ－ＣＤＯ－ＭｅＢ只有在ｐＨ＝３．５－４．０时标记率才能大于９０％。小鼠体内分布实验表明，＾９９ｍＴｃ－ＣＤＯ－ＭｅＢ在动物心肌中较高的吸收，但随时间延长而迅速清除。心／肝比值在给药后１、５和１０ｍｉｎ时分别为３、１．５和０．８。＾９９ｍＴｃ－ＣＤＯ在心、脑中的浓聚明显低于９９ｍＴｃ－ＣＤＯ－ＭｅＢ。     

^99mTc—MIBI心肌灌注显像潘生丁试验一天法在冠心病诊断中的应用

介绍了对１６１例冠心病患者采用＾９９ｍＴｃ－ＭＩＢＩ心肌显像潘生丁试验一天法方案进行检测的结果，其中２０例与冠状动脉造影进行了对比观察。患者先作＾９９ｍＴｃ－ＭＩＢＩ静态平面与断层心肌显像，接着进行潘生丁试验，再于静脉注射＾９９ｍＴｃ－ＭＩＢＩ后１ｈ作平面与断层心肌显像。采用本方法诊断冠心病的灵敏度为９１％。其检测ＬＡＤ的灵敏度为８８％；诊断ＲＣＡ及Ｌｃｘ的灵敏度分别为８１％与７７％、特异性分别为     

^125I—抗Tg—McAb与甲状腺癌细胞结合的体外实验研究

选用自制的１８Ａ１和１８Ａ１１两株ＭｃＡｂ进行体外活细胞结合实验,定量观察＾１２５Ｉ标记的１８Ａ１和１８Ａ１１与正常甲状腺组织细胞及某些肿瘤细胞膜结合的反应性。实验结果显示,＾１２５Ｉ－抗Ｔｇ－ＭｃＡｂ与高分化甲癌细胞的结合率均〉３０％;与髓样癌结合率为８％－１２％;与正常甲状腺和甲状腺良性瘤细胞结合率〈１０％;其他细胞均〈４％。碘标记ＭｃＡｂ与正常甲状腺和甲状腺良性瘤细胞的结合率显著低于高分化甲     

99Tcm直接法标记Octreotide

建立了＾９９Ｔｃ＾ｍ直接标记Ｏｃｔｒｅｏｔｉｄｅ的方法，并选出了最佳标记条件。在最佳标记条件下，标记率为７８．６％，纯化后放化纯度为９３．８％。纯化后的标记物室温下放置４ｈ，或分别与过量ＤＴＰＡ、ＨＳＡ和Ｌ－半胱氨酸３７℃孵育４ｈ，其放化纯度为９２．１％￣９３．６％，无显著改变。＾９９Ｔｃ＾ｍ直接标记Ｏｃｔｒｅｏｔｉｄｅ方法可行，标记肽稳定性好，可望用于生长抑素受体显像。     

99mTc直接法标记抗体的3个常用还原剂的评价

比较了＾９９ｍＴｃ直接法标记抗体的３个常用的还原剂：氯化亚锡（ＳｎＣｌ２），２－疏工乙醇（２－ＭＥ）和抗坏血酸（ＡＡ）的＾９９ｍＴｃ标记率、标记抗体的稳定性及免疫活性。结果显示，２－ＭＥ是一个良好的还原剂，当抗体／２－ＭＥ摩尔比为１：２０００时，抗体的标记率可达到９５％以上，胶体形成量少于５％，＾９９ｍＴｃ－ＢＡＣ５肿瘤放射免疫显像，鼻咽癌转移癌影像清晰。     

一种新型骨显像剂^99Tc^m—AEDP的初步研究

本文着重研究了以氯化亚锡为还原剂，用＾９９Ｔｃ＾ｍ标记ＡＥＤＰ的条件，即Ｓｎ（Ⅱ）含量、标记时间、葡萄糖和抗坏血酸以及ｐＨ以标记率的影响，确定了最佳标记条件。实验结果表明，＾９９Ｔｃ＾ｍ－ＡＥＤＰ标记率〉９５％，标记后４ｈ内放化纯度保持不变。小鼠体内分布及家兔显像均与＾９９Ｔｃ＾ｍ－ＭＤＰ相当，ＡＥＤＰ稳定性好，合成简便，是一种值得进一步深入研究的骨显像剂。     

小剂量照射的淋巴细胞外液诱导其亚群细胞DNA合成…

预先给予４．０ｃＧｙγ射线照射的人外周血淋巴细胞，经ＰＨＡ刺激２４ｈ后提取细胞外液，观察其对大剂量照射后受损伤的亚群细胞的影响。结果表明，ＣＤ＾＋８，ＣＤ＾＋４细胞损伤明显减轻，且损伤剂量分别为１．５，３．０Ｇｙ时，适应性反应最强。结果还显示，ＣＤ＾＋８细胞较ＣＤ＾＋４细胞对辐射更敏感，     

A comparative study of primary coronary stenting and intravenous thrombolysis for acute myocardial infarction using ^99mTc-MIBI SPECT imaging

1 INTRODUCTIONRe-perfusion therapy is one of the important progresses of acute myocardial infarction (AMI) therapy. It is established that early intravenous thrombolysis is effective and convenient for patency-related artery (IRA)[']. But obvious limitation existsfor thrombolysis application such as low IRA patency rate, recuxrent ischeAnc events,high re-infarction rate, hemorrhage complication and so many contraindications. Recentyearst primary coronary steming has been developed as …     

β甲基对125碘苯代十五烷酸(125I-BMIPP)的初步动物实验

为了解脂肪酸代谢显像剂 β甲基对12 5碘苯代十五烷酸 (12 5I -BMIPP)在动物体内的分布、清除和代谢干预对其心肌摄取的变化等行为 ,进行了12 5I -BMIPP的动物研究。结果显示 ,禁食SD大鼠心肌对12 5I -BMIPP的摄取高 ,最大吸收值为 5 .70 %/ g ,在心肌中滞留 1h都不变 ,至12 0min心肌摄取仍高达 2 .19± 0 .4 2ID %/ g ;30min心 /血、心 /肝和心 /肺比分别为 3.4 0、2 .6 4和 2 .88;12 5I-BMIPP在肝、肺中的摄取低 ,排泄快 ;甲状腺摄取低 ,至 12 0min ,甲状腺摄取值为 0 .0 2ID %/g ;12 5I-BMIPP与小鼠体内、外血浆蛋白结合稳定 ;异常毒性试验合格 ,每千克小鼠接受的量是人的 5 0 0倍 ;pH为 7.0 0和 7.4 0时的分配系数 (logP)分别为 1.93和 1.6 8;代谢干预研究结果显示 ,葡萄糖胰岛素干预组心肌摄取明显升高 ,与对照组相比差异具有极显著的意义。     

99mTc标记新型硼酸结构快速心肌灌注显像药物的制备及初步显像评价

^99mTc-TEBO为临床批准的快速心肌灌注显像药物,该药物初始摄取高,但心肌滞留不稳定,为此,本研究通过优化其硼酸结构,分别制备标记物^99mTc-2SP、^99mTc-4LPA及^99mTc-2MDM,制备时间均为30 min,均为无色澄明液体,放化纯度均>95%,分别在健康小型猪体内进行SPECT动态显像,并与99mTc TEBO进行对比。结果表明：^99mTc-TEBO注射后0~5 min,左室心肌快速摄取,但随后心肌放射性迅速洗脱,在10 min时心肌约洗脱至峰值的75%,与心血池放射性浓度比值为1.63。^99mTc-2SP引入2-甲磺酰基吡啶-5-硼酸基后心肌初始摄取高,心肌滞留时间明显延长,心肌洗脱较缓慢,左室心肌均清晰显影,在第10 min时心肌摄取仍可保持峰值的95%,与心血池放射性浓度比值为3.75,明显高于^99mTc-TEBO。而另外两种显像剂^99mTc-4LPA和^99mTc-2MDM在注射后15 min内显像不理想。因此,^99mTc-2SP是有潜力的心肌灌注显像药物。     

99Tcm标记NGR及其在荷人HePG2肝癌裸鼠体内的生物分布及SPECT显像

用⁹⁹Tc^m标记了含有天冬酰胺-甘氨酸-精氨酸（Asn-Gly-Arg）序列的血管靶向性短肽NGR,评价了标记物⁹⁹Tc^m-NGR的放化性质以及在荷HePG2肝癌模型裸鼠体内的生物分布和SPECT显像。标记结果显示,⁹⁹Tc^m-NGR的标记率>90%,放化纯度>95%。荷瘤裸鼠体内生物分布结果显示,⁹⁹Tc^m-NGR在肾脏和肝脏的摄取率较高,注射后1 h肿瘤摄取达（2.52±0.62）%ID/g,最高达（7.26±2.71）%ID/g,12 h仍然达（3.93±1.93）%ID/g,但在竞争性抑制组中摄取率为（1.29±0.85）%ID/g。荷瘤裸鼠的SPECT显像结果显示,除肿瘤外,其他组织器官的放射性摄取随时间延长逐渐降低,肿瘤与肌肉组织的放射性攝取比（T/NT）4 h时最高,可达3.25。注射后1 h肿瘤可见,12 h时最为清晰。以上结果提示,⁹⁹Tc^m-NGR易于制备,具有良好的靶向性, 在肿瘤的诊疗中具有良好的研究前景。     

Preclinical pharmacology study of neutral myocardial imaging agent ^99mTcN（NOEt）2

To explore the biological properties of a new neutral myocardial imaging agent ^99mTcN(NOEt)2,preparation and characterization of ^99mTcN(NOEt)2, kinetics of blood-drug clearance in rabbits,biodistribution in rats,test of undue toxicity in mice and myocardial imaging in dogs were performed and volunteer imaging,Radiochemical purity of 99m TcN(NOEt)2 was over than90% and stable for 6 hours at room temperature.Blood disappearance was analyzed with biexponential model,T1/2(α)=2.53min,T1/2(β)=330min and Cl=378mL/h were obtained.Biodistribution studies demonstrated that ^99mTcN(NOEt)2 localized selectively in myocardium of rats.Cardiac uptake were 2.79,2.25,2.00 and 1.88%ID/organ at 5,30,60 and 90min of postinjection,respectively.The heart-to-lung activity ratio was 1.16 at 60 min.Images showed that pulmonary uptake decreased faster than cardiac uptake in a dog.The mean heart-to-lung activity ratios in a dog were 1.69,2.40and 2.55at 10,30and 60min of postinjection,respectively.The heart was distinguishable on scans at 30min.Whole body imaging showed that cardiac uptake was 2.82%ID at 90min,but hepatic uptake was 30%ID and remained constant.The test of undue toxicity showed that the dose received by mice was 614 times as by human.Volunteer imaging suggests ^99mTcN(NOEt)2 redistribution with time.^99mTcN(NOEt)2 exhibited favorable stabilities,biological properties and safety,It is worth for further studying in human.     

Preparation andBiodistribution of Myocardial Perfusion Imaging Agent 18F-TPT

⁹⁹Tc^m-sestamibi is typically used as amyocardial perfusion imaging agent for SPECT, however, the high uptake of liverand lung compromise the diagnostic accuracy. PET has higher spatial resolutionand quantitative measurement of myocardial tracer uptake. The lipophiliccationic compound, (4-[¹⁸F]fluorophenyl)triphenylphosphoniumion (¹⁸F-TPT)was synthesized as a potential positron emission tomography (PET) myocardialperfusion agent, biodistribution studies in the NH rats and Micro PET/CTimaging studies in the SD rats were performed. Total synthesis time was about 1h and the uncorrected synthesis yield was 2.5%, radiochemical purity was higherthan 99.5%, the product had good stability at room temperature. Biodistributiondata in rats showed high levels of accumulation in the heart with stableretention and rapid blood clearance, Heart-to-liver ratios at 30, 60, 90,and120 min were 33.1, 14.8, 25.7 and 17.3, respectively; Micro PET/CT imagingin the SD rat showed intense cardiac uptake and non-target tissues as liver,lung uptake were washed out quickly. The result show that ¹⁸F-TPT may have potential as amyocardial perfusion imaging agent for PET.     

18F-FDG PET/CT显像对心肌“缺血记忆”的分子机制研究

建立了不同程度的犬急性心肌缺血-再灌注模型。利用¹⁸F-FDG PET/CT动态心肌显像和实时定量PCR方法探讨了缺血心肌葡萄糖代谢改变（缺血记忆）和缺血程度的关系。将8只杂种犬随机分为球囊封堵20 min组（4只）和40 min组（4只）,在空腹状态下（禁食>12 h）行基础、缺血1 h和缺血24 h的¹⁸F-FDG PET/CT动态心肌显像以及⁹⁹Tc^m-MIBI SPECT心肌灌注显像。计算缺血区和非缺血区心肌的葡萄糖摄取率比值K。所有显像完成后处死实验犬并分别取缺血区、非缺血区心肌组织。应用实时定量PCR方法,测定葡萄糖转运体蛋白1、4（GLUT-1、GLUT-4）、心脏脂肪酸结合蛋白（H-FABP）基因的mRNA表达量。两组犬三次心肌灌注显像均未见异常。基础显像时,两组预封堵心肌与非缺血区心肌¹⁸F-FDG摄取率的比值K无明显差异;缺血1 h后,两组K值均增加,且40 min组高于20 min组;缺血24 h后,40 min组的K值仍高于基础状态,而20 min组的K值与基础状态下无明显差异。PCR结果示,两组非缺血心肌的GLUT-1、GLUT-4以及H-FABP基因mRNA表达量无明显差异,而缺血心肌的GLUT-1和GLUT-4基因mRNA表达量增加,H-FABP基因的mRNA表达量减低,且40 min组的改变较20 min组更为明显。以上结果提示,心肌缺血-再灌注后,缺血心肌对葡萄糖（¹⁸F-FDG）摄取增加的程度和持续时间（缺血记忆）与缺血的程度相关。     

99Tcm-抗纤维蛋白单克隆抗体对兔动静脉血栓的放免显像

The anti-fibrin McAb SZ-63 is labeled by using the method of 2-iminothiolane modification and ⁹⁹Tc^m-glucoheptonate(GH) transchelation. The experimental femoral arterial and venous thrombi are prepared in rabbits, then ⁹⁹Tc^m-SZ-63 is injected into ear-edge vein and imaged by SPECT. ⁹⁹Tc^m-labeled murine IgG is used as a negative control. The old arterial and venous thrombi in rabbits are clearly imaged 2 to 4 h after injection of ⁹⁹Tc^m-SZ-63. McAb SZ-63 would be a potential agent for diagnosis and therapy of thrombotic disease.     

特异性前哨淋巴结显像剂99Tcm-rituximab药盒的制备及生物评价

采用2-巯基乙醇修饰Rituximab（利妥昔单克隆抗体）,制得其冻干药盒。所制得的冻干药盒性质稳定,可在-20 ℃冷冻保存3个月以上。利用⁹⁹Tc^m-葡庚糖酸钠（GH）交换法,标记冻干药盒得到⁹⁹Tc^m-rituximab,标记率和放化纯度均大于90%。生物分布结果显示：SD大鼠经前脚掌皮下注射⁹⁹Tc^m-rituximab后,前哨淋巴结的摄取值在1~4 h内逐渐增加,在4 h时达到（2.14±0.46）%ID,前哨淋巴结与注射点的放射性摄取比在4 h时达到最大（14.80%±2.11%）,且在18 h时,这一比值基本保持不变。SPECT显像结果表明,在30 min~18 h内,大鼠的前哨淋巴结清晰可见,无次级淋巴结显影。本研究提供了一种特异性前哨淋巴结显像剂的药盒化制备方法,该方法操作简便,性能稳定,便于在临床推广应用。